mitochondria

Summary

Summary: Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)

Top Publications

  1. ncbi The biochemistry of apoptosis
    M O Hengartner
    Cold Spring Harbor Laboratory, New York 11724, USA
    Nature 407:770-6. 2000
  2. pmc PINK1-dependent recruitment of Parkin to mitochondria in mitophagy
    Cristofol Vives-Bauza
    Department of Neurology, Columbia University, New York, NY 10032, USA
    Proc Natl Acad Sci U S A 107:378-83. 2010
  3. ncbi The BCL-2 protein family: opposing activities that mediate cell death
    Richard J Youle
    Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, The National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Rev Mol Cell Biol 9:47-59. 2008
  4. ncbi Cell death: critical control points
    Nika N Danial
    Howard Hughes Medical Institute, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Cell 116:205-19. 2004
  5. doi A role for mitochondria in NLRP3 inflammasome activation
    Rongbin Zhou
    Department of Biochemistry, Center of Immunity and Infection, University of Lausanne, Chemin des Boveresses 155, CH 1066 Epalinges, Switzerland
    Nature 469:221-5. 2011
  6. ncbi The pathobiology of diabetic complications: a unifying mechanism
    Michael Brownlee
    Departments of Medicine and Pathology, Albert Einstein College of Medicine, F 531 1300 Morris Park Ave, Bronx, NY 10461 1602, USA
    Diabetes 54:1615-25. 2005
  7. pmc Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death
    M C Wei
    Howard Hughes Medical Institute, Departments of Pathology and Medicine, Harvard Medical School, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Science 292:727-30. 2001
  8. pmc A mitochondrial protein compendium elucidates complex I disease biology
    David J Pagliarini
    Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA
    Cell 134:112-23. 2008
  9. pmc How mitochondria produce reactive oxygen species
    Michael P Murphy
    MRC Dunn Human Nutrition Unit, Hills Road, Cambridge CB20XY, UK
    Biochem J 417:1-13. 2009
  10. doi Lysine acetylation targets protein complexes and co-regulates major cellular functions
    Chunaram Choudhary
    Proteomics and Signal Transduction, Max Planck Institute for Biochemistry, Martinsried, Germany
    Science 325:834-40. 2009

Detail Information

Publications372 found, 100 shown here

  1. ncbi The biochemistry of apoptosis
    M O Hengartner
    Cold Spring Harbor Laboratory, New York 11724, USA
    Nature 407:770-6. 2000
    ..Here I review the basic components of the death machinery, describe how they interact to regulate apoptosis in a coordinated manner, and discuss the main pathways that are used to activate cell death...
  2. pmc PINK1-dependent recruitment of Parkin to mitochondria in mitophagy
    Cristofol Vives-Bauza
    Department of Neurology, Columbia University, New York, NY 10032, USA
    Proc Natl Acad Sci U S A 107:378-83. 2010
    ..membrane potential (DeltaPsi(m)) in human cells, cytosolic Parkin has been reported to be recruited to mitochondria, which is followed by a stimulation of mitochondrial autophagy...
  3. ncbi The BCL-2 protein family: opposing activities that mediate cell death
    Richard J Youle
    Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, The National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Rev Mol Cell Biol 9:47-59. 2008
    ..Although these insights into interactions among BCL-2 family proteins reveal how these proteins are regulated, a unifying hypothesis for the mechanisms they use to activate caspases remains elusive...
  4. ncbi Cell death: critical control points
    Nika N Danial
    Howard Hughes Medical Institute, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Cell 116:205-19. 2004
    ..The identification of critical control points in the cell death pathway has yielded fundamental insights for basic biology, as well as provided rational targets for new therapeutics...
  5. doi A role for mitochondria in NLRP3 inflammasome activation
    Rongbin Zhou
    Department of Biochemistry, Center of Immunity and Infection, University of Lausanne, Chemin des Boveresses 155, CH 1066 Epalinges, Switzerland
    Nature 469:221-5. 2011
    ..Here we show that mitophagy/autophagy blockade leads to the accumulation of damaged, ROS-generating mitochondria, and this in turn activates the NLRP3 inflammasome...
  6. ncbi The pathobiology of diabetic complications: a unifying mechanism
    Michael Brownlee
    Departments of Medicine and Pathology, Albert Einstein College of Medicine, F 531 1300 Morris Park Ave, Bronx, NY 10461 1602, USA
    Diabetes 54:1615-25. 2005
  7. pmc Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death
    M C Wei
    Howard Hughes Medical Institute, Departments of Pathology and Medicine, Harvard Medical School, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Science 292:727-30. 2001
    Multiple death signals influence mitochondria during apoptosis, yet the critical initiating event for mitochondrial dysfunction in vivo has been unclear...
  8. pmc A mitochondrial protein compendium elucidates complex I disease biology
    David J Pagliarini
    Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA
    Cell 134:112-23. 2008
    b>Mitochondria are complex organelles whose dysfunction underlies a broad spectrum of human diseases...
  9. pmc How mitochondria produce reactive oxygen species
    Michael P Murphy
    MRC Dunn Human Nutrition Unit, Hills Road, Cambridge CB20XY, UK
    Biochem J 417:1-13. 2009
    The production of ROS (reactive oxygen species) by mammalian mitochondria is important because it underlies oxidative damage in many pathologies and contributes to retrograde redox signalling from the organelle to the cytosol and nucleus...
  10. doi Lysine acetylation targets protein complexes and co-regulates major cellular functions
    Chunaram Choudhary
    Proteomics and Signal Transduction, Max Planck Institute for Biochemistry, Martinsried, Germany
    Science 325:834-40. 2009
    ..Our data demonstrate that the regulatory scope of lysine acetylation is broad and comparable with that of other major posttranslational modifications...
  11. doi Mitochondria and cell death: outer membrane permeabilization and beyond
    Stephen W G Tait
    Department of Immunology, St Jude Childrens Research Hospital, Memphis, Tennessee 38105, USA
    Nat Rev Mol Cell Biol 11:621-32. 2010
    ..MOMP typically leads to cell death irrespective of caspase activity by causing a progressive decline in mitochondrial function, although cells can survive this under certain circumstances, which may have pathophysiological consequences...
  12. ncbi Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis
    H Li
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cell 94:491-501. 1998
    ..While full-length BID is localized in cytosol, truncated BID (tBID) translocates to mitochondria and thus transduces apoptotic signals from cytoplasmic membrane to mitochondria...
  13. pmc Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin
    Atsushi Tanaka
    Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA
    J Cell Biol 191:1367-80. 2010
    Damage to mitochondria can lead to the depolarization of the inner mitochondrial membrane, thereby sensitizing impaired mitochondria for selective elimination by autophagy...
  14. ncbi The pathophysiology of mitochondrial cell death
    Douglas R Green
    Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92121, USA
    Science 305:626-9. 2004
    ..Numerous pro-apoptotic signal-transducing molecules and pathological stimuli converge on mitochondria to induce MOMP...
  15. pmc Fission and selective fusion govern mitochondrial segregation and elimination by autophagy
    Gilad Twig
    Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA
    EMBO J 27:433-46. 2008
    Accumulation of depolarized mitochondria within beta-cells has been associated with oxidative damage and development of diabetes...
  16. pmc A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter
    Diego De Stefani
    Department of Biomedical Science, University of Padua, 35121 Padua, Italy
    Nature 476:336-40. 2011
    ....
  17. pmc Metabolic reprogramming: a cancer hallmark even warburg did not anticipate
    Patrick S Ward
    Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Cancer Cell 21:297-308. 2012
    ..Despite these early beliefs, the metabolic signatures of cancer cells are not passive responses to damaged mitochondria but result from oncogene-directed metabolic reprogramming required to support anabolic growth...
  18. doi Tumor cell metabolism: cancer's Achilles' heel
    Guido Kroemer
    INSERM, U848, F 94805 Villejuif, France
    Cancer Cell 13:472-82. 2008
    ..As an example, the resistance of cancer mitochondria against apoptosis-associated permeabilization and the altered contribution of these organelles to metabolism ..
  19. pmc Autophagy, mitochondria and oxidative stress: cross-talk and redox signalling
    Jisun Lee
    Center for Free Radical Biology, University of Alabama at Birmingham, 901 19th Street South, Birmingham, AL 35294, USA
    Biochem J 441:523-40. 2012
    ..At low levels, they are signalling molecules, and at high levels, they damage organelles, particularly the mitochondria. Oxidative damage and the associated mitochondrial dysfunction may result in energy depletion, accumulation of ..
  20. ncbi A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth
    Sebastien Bonnet
    Pulmonary Hypertension Program and Vascular Biology Group, Department of Physiology, University of Alberta, Edmonton, AB T6G 2B7, Canada
    Cancer Cell 11:37-51. 2007
    ..Molecular inhibition of PDK2 by siRNA mimics DCA. The mitochondria-NFAT-Kv axis and PDK are important therapeutic targets in cancer; the orally available DCA is a promising ..
  21. pmc Mitochondrial fission, fusion, and stress
    Richard J Youle
    Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA
    Science 337:1062-5. 2012
    Mitochondrial fission and fusion play critical roles in maintaining functional mitochondria when cells experience metabolic or environmental stresses...
  22. pmc Inhibition of macroautophagy triggers apoptosis
    Patricia Boya
    CNRS UMR 8125, Institut Gustave Roussy, Pavillon de Recherche 1, 39 rue Camille Desmoulins, F 94805 Villejuif, France
    Mol Cell Biol 25:1025-40. 2005
    ..All together, these data indicate that autophagy may be cytoprotective, at least under conditions of nutrient depletion, and point to an important cross talk between type 1 and type 2 cell death pathways...
  23. doi Mitofusin 2 tethers endoplasmic reticulum to mitochondria
    Olga Martins de Brito
    Dulbecco Telethon Institute, Venetian Institute of Molecular Medicine, Via Orus 2, 35129 Padova, Italy
    Nature 456:605-10. 2008
    Juxtaposition between endoplasmic reticulum (ER) and mitochondria is a common structural feature, providing the physical basis for intercommunication during Ca(2+) signalling; yet, the molecular mechanisms controlling this interaction are ..
  24. pmc Telomere dysfunction induces metabolic and mitochondrial compromise
    Ergun Sahin
    Belfer Institute for Applied Cancer Science, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Nature 470:359-65. 2011
    ..We propose that this telomere-p53-PGC axis contributes to organ and metabolic failure and to diminishing organismal fitness in the setting of telomere dysfunction...
  25. pmc Mitochondria supply membranes for autophagosome biogenesis during starvation
    Dale W Hailey
    The Eunice Kennedy Shriver National Institutes of Child Health and Human Development, 18 Library Drive, Bethesda, MD 20892, USA
    Cell 141:656-67. 2010
    ..Here, we demonstrate that, in starved cells, the outer membrane of mitochondria participates in autophagosome biogenesis...
  26. pmc Mechanisms of mitophagy
    Richard J Youle
    Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 35 Convent Drive, 2C 917, Bethesda, Maryland 20892, USA
    Nat Rev Mol Cell Biol 12:9-14. 2011
    ..Mitophagy, the specific autophagic elimination of mitochondria, has been identified in yeast, mediated by autophagy-related 32 (Atg32), and in mammals during red blood cell ..
  27. pmc Parkin is recruited selectively to impaired mitochondria and promotes their autophagy
    Derek Narendra
    Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA
    J Cell Biol 183:795-803. 2008
    ..the role of Parkin in neuron maintenance is unknown, recent work has linked Parkin to the regulation of mitochondria. Its loss is associated with swollen mitochondria and muscle degeneration in Drosophila melanogaster, as well ..
  28. ncbi Mitochondrial dysfunction and type 2 diabetes
    Bradford B Lowell
    Department of Medicine, Beth Israel Deaconess Medical Center, 99 Brookline Avenue, Harvard Medical School, Boston, MA 02215, USA
    Science 307:384-7. 2005
    ..Emerging evidence supports the potentially unifying hypothesis that both of these prominent features of type 2 diabetes are caused by mitochondrial dysfunction...
  29. pmc Mitochondria: the next (neurode)generation
    Eric A Schon
    Department of Neurology, Columbia University, New York, NY 10032, USA
    Neuron 70:1033-53. 2011
    ..These new mechanisms by which mitochondria may also be linked to neurodegeneration will likely have far-reaching implications for our understanding of the ..
  30. pmc Nix is a selective autophagy receptor for mitochondrial clearance
    Ivana Novak
    Mediterranean Institute for Life Sciences, Mestrovicevo setaliste bb, HR 21000 Split, Croatia
    EMBO Rep 11:45-51. 2010
    ..In cultured cells, Nix recruits GABARAP-L1 to damaged mitochondria through its amino-terminal LC3-interacting region...
  31. doi Autophagosomes form at ER-mitochondria contact sites
    Maho Hamasaki
    Department of Genetics, Graduate School of Medicine, Osaka University, 2 2 Yamadaoka, Suita, Osaka 565 0871, Japan
    Nature 495:389-93. 2013
    ..is much controversy about the organelle from which the membranes originate--the endoplasmic reticulum (ER), mitochondria and plasma membrane...
  32. ncbi Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy
    Sophie Pattingre
    Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    Cell 122:927-39. 2005
    ..This antiautophagy function of Bcl-2 may help maintain autophagy at levels that are compatible with cell survival, rather than cell death...
  33. ncbi The incomplete natural history of mitochondria
    J William O Ballard
    Department of Biological Sciences, University of Iowa, Iowa City, Iowa 52242, USA
    Mol Ecol 13:729-44. 2004
    ..This review has four sections. First, we review aspects of the natural history of mitochondria and their DNA to show that it is a unique molecule with specific characteristics that differ from nuclear DNA...
  34. ncbi Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin
    Ira E Clark
    Nature 441:1162-6. 2006
    ..Pink1 localizes to mitochondria, and mitochondrial cristae are fragmented in pink1 mutants...
  35. pmc Mitochondrial dynamics--fusion, fission, movement, and mitophagy--in neurodegenerative diseases
    Hsiuchen Chen
    Division of Biology and Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA
    Hum Mol Genet 18:R169-76. 2009
    ..Recent discoveries have highlighted that neurons are reliant particularly on the dynamic properties of mitochondria. Mitochondria are dynamic organelles by several criteria...
  36. doi Mitochondria: in sickness and in health
    Jodi Nunnari
    Department of Molecular and Cellular Biology, University of California, Davis, Davis, CA 95616, USA
    Cell 148:1145-59. 2012
    b>Mitochondria perform diverse yet interconnected functions, producing ATP and many biosynthetic intermediates while also contributing to cellular stress responses such as autophagy and apoptosis...
  37. doi The role of mitochondria in cellular iron-sulfur protein biogenesis and iron metabolism
    Roland Lill
    Institut für Zytobiologie und Zytopathologie, Philipps Universitat Marburg, Robert Koch Str 6, 35033 Marburg, Germany
    Biochim Biophys Acta 1823:1491-508. 2012
    b>Mitochondria play a key role in iron metabolism in that they synthesize heme, assemble iron-sulfur (Fe/S) proteins, and participate in cellular iron regulation. Here, we review the latter two topics and their intimate connection...
  38. pmc Cytoplasmic functions of the tumour suppressor p53
    Douglas R Green
    Department of Immunology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Nature 458:1127-30. 2009
    ..An emerging area of research unravels additional activities of p53 in the cytoplasm, where it triggers apoptosis and inhibits autophagy. These previously unknown functions contribute to the mission of p53 as a tumour suppressor...
  39. ncbi Regulation of cell death: the calcium-apoptosis link
    Sten Orrenius
    Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, Box 210, SE 171 77 Stockholm, Sweden
    Nat Rev Mol Cell Biol 4:552-65. 2003
    ..However, more recently it has become clear that cellular Ca2+ overload, or perturbation of intracellular Ca2+ compartmentalization, can cause cytotoxicity and trigger either apoptotic or necrotic cell death...
  40. ncbi Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis
    Jerry E Chipuk
    Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92121, USA
    Science 303:1010-4. 2004
    ..p53 directly activated the proapoptotic Bcl-2 protein Bax in the absence of other proteins to permeabilize mitochondria and engage the apoptotic program...
  41. pmc Dynamin-related protein Drp1 is required for mitochondrial division in mammalian cells
    E Smirnova
    Department of Biological Chemistry, UCLA School of Medicine, Los Angeles, California 90095 1737, USA
    Mol Biol Cell 12:2245-56. 2001
    Mutations in the human dynamin-related protein Drp1 cause mitochondria to form perinuclear clusters. We show here that these mitochondrial clusters consist of highly interconnected mitochondrial tubules...
  42. doi Transcriptional paradigms in mammalian mitochondrial biogenesis and function
    Richard C Scarpulla
    Department of Cell and Molecular Biology, Northwestern Medical School, Chicago, Illinois 60611, USA
    Physiol Rev 88:611-38. 2008
    b>Mitochondria contain their own genetic system and undergo a unique mode of cytoplasmic inheritance. Each organelle has multiple copies of a covalently closed circular DNA genome (mtDNA)...
  43. doi A role for ubiquitin in selective autophagy
    Vladimir Kirkin
    Institute of Biochemistry II and Cluster of Excellence Macromolecular Complexes, Goethe University, Theodor Stern Kai 7, Frankfurt, Germany
    Mol Cell 34:259-69. 2009
    ..This review explores the hypothesis that ubiquitin represents a selective degradation signal suitable for targeting various types of cargo, ranging from protein aggregates to membrane-bound organelles and microbes...
  44. ncbi Molecular characterization of mitochondrial apoptosis-inducing factor
    S A Susin
    Centre National de la Recherche Scientifique, UPR 420, Villejuif, France
    Nature 397:441-6. 1999
    b>Mitochondria play a key part in the regulation of apoptosis (cell death). Their intermembrane space contains several proteins that are liberated through the outer membrane in order to participate in the degradation phase of apoptosis...
  45. ncbi Premature ageing in mice expressing defective mitochondrial DNA polymerase
    Aleksandra Trifunovic
    Department of Medical Nutrition, Karolinska Institutet, Novum, Karolinska University Hospital, S 141 86 Stockholm, Sweden
    Nature 429:417-23. 2004
    ..Our results thus provide a causative link between mtDNA mutations and ageing phenotypes in mammals...
  46. ncbi BCL-2 family members and the mitochondria in apoptosis
    A Gross
    Department of Pathology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Genes Dev 13:1899-911. 1999
  47. pmc Selective autophagy mediated by autophagic adapter proteins
    Terje Johansen
    Molecular Cancer Research Group, Institute of Medical Biology, University of Tromsø, Tromsø, Norway
    Autophagy 7:279-96. 2011
    ..autophagy in mammalian cells discussing the degradation of misfolded proteins, p62 bodies, aggresomes, mitochondria and invading bacteria...
  48. pmc Assessing mitochondrial dysfunction in cells
    Martin D Brand
    Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA 94945, USA
    Biochem J 435:297-312. 2011
    ..Usually, it is the ability of the mitochondria to make ATP appropriately in response to energy demands...
  49. pmc Mitochondrial nucleoid interacting proteins support mitochondrial protein synthesis
    J He
    MRC Mitochondrial Biology Unit, Wellcome Trust MRC Building, Hills Road Cambridge, CB2 0XY, UK
    Nucleic Acids Res 40:6109-21. 2012
    ..These findings suggest an intimate association between nucleoids and the machinery of protein synthesis in mitochondria. ATAD3 and prohibitin are tightly associated with the mitochondrial membranes and so we propose that they ..
  50. pmc Mitochondria in apoptosis: Bcl-2 family members and mitochondrial dynamics
    Jean Claude Martinou
    Department of Cell Biology, University of Geneva, Faculty of Sciences, 30 Quai Ernest Ansermet, Geneva 4, Switzerland
    Dev Cell 21:92-101. 2011
    b>Mitochondria participate in apoptosis through a range of mechanisms that vary between vertebrates and invertebrates...
  51. pmc Mitochondrial dysfunction in Parkinson's disease: molecular mechanisms and pathophysiological consequences
    Nicole Exner
    Biochemistry, Adolf Butenandt Institute, Ludwig Maximilians University, Munich, Germany
    EMBO J 31:3038-62. 2012
    ..The dimensions and polarity of neurons require efficient transport of mitochondria to hot spots of energy consumption, such as presynaptic and postsynaptic sites...
  52. pmc Drosophila parkin requires PINK1 for mitochondrial translocation and ubiquitinates mitofusin
    Elena Ziviani
    Department of Biomedical Sciences, Medical Research Council Centre for Developmental and Biomedical Genetics, University of Sheffield, Sheffield S10 2TN, United Kingdom
    Proc Natl Acad Sci U S A 107:5018-23. 2010
    ..Recent evidence suggests that Parkin is recruited to damaged mitochondria, possibly affecting mitochondrial fission and/or fusion, to mediate their autophagic turnover...
  53. pmc Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes
    Robert B Hamanaka
    Department of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University Medical School, Chicago, IL 60611, USA
    Trends Biochem Sci 35:505-13. 2010
    ..Production of ROS at mitochondria thus integrates cellular energy state, metabolite concentrations, and other upstream signaling events and has ..
  54. pmc Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1
    Jaime N Guzman
    Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
    Nature 468:696-700. 2010
    ..Because drugs approved for human use can antagonize calcium entry through L-type channels, these results point to a novel neuroprotective strategy for both idiopathic and familial forms of Parkinson's disease...
  55. doi Regulation of autophagy by ROS: physiology and pathology
    Ruth Scherz-Shouval
    Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, 76100, Israel
    Trends Biochem Sci 36:30-8. 2011
    ..Notably, recent advances in the field of redox regulation of autophagy focus on the role of mitochondria as a source of ROS and on mitophagy as a means for clearance of ROS.
  56. ncbi Mitochondrial diseases in man and mouse
    D C Wallace
    Center for Molecular Medicine, Emory University, 1462 Clifton Road, Suite 420, Atlanta, GA 30322, USA
    Science 283:1482-8. 1999
    ..The importance and interrelationship of these functions are now being studied in mouse models of mitochondrial disease...
  57. doi Molecular mechanisms of necroptosis: an ordered cellular explosion
    Peter Vandenabeele
    Department for Molecular Biomedical Research, VIB, Ghent University, Belgium
    Nat Rev Mol Cell Biol 11:700-14. 2010
    ..Necroptosis participates in the pathogenesis of diseases, including ischaemic injury, neurodegeneration and viral infection, thereby representing an attractive target for the avoidance of unwarranted cell death...
  58. ncbi An inhibitor of Bcl-2 family proteins induces regression of solid tumours
    Tilman Oltersdorf
    Idun Pharmaceuticals, 9380 Judicial Drive, San Diego, California 92121, USA
    Nature 435:677-81. 2005
    ....
  59. ncbi Mitochondria, oxidants, and aging
    Robert S Balaban
    Laboratory of Cardiac Energetics, National Institutes of Health, Bethesda, Maryland 20892, USA
    Cell 120:483-95. 2005
    ..Here we review the evidence that both supports and conflicts with the free radical theory and examine the growing link between mitochondrial metabolism, oxidant formation, and the biology of aging...
  60. pmc Mitochondria and the autophagy-inflammation-cell death axis in organismal aging
    Douglas R Green
    Department of Immunology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Science 333:1109-12. 2011
    Alterations of mitochondrial functions are linked to multiple degenerative or acute diseases. As mitochondria age in our cells, they become progressively inefficient and potentially toxic, and acute damage can trigger the permeabilization ..
  61. pmc AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha
    Sibylle Jäger
    Dana Farber Cancer Institute, Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 104:12017-22. 2007
    ..These data indicate that AMPK phosphorylation of PGC-1alpha initiates many of the important gene regulatory functions of AMPK in skeletal muscle...
  62. pmc Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction
    Shinichi Someya
    Departments of Genetics and Medical Genetics, University of Wisconsin, Madison, 53706, USA
    Cell 143:802-12. 2010
    ..2 (Idh2), leading to increased NADPH levels and an increased ratio of reduced-to-oxidized glutathione in mitochondria. In cultured cells, overexpression of Sirt3 and/or Idh2 increases NADPH levels and protects from oxidative ..
  63. pmc Importing mitochondrial proteins: machineries and mechanisms
    Agnieszka Chacinska
    Institut fur Biochemie und Molekularbiologie, ZBMZ, Universitat Freiburg, 79104 Freiburg, Germany
    Cell 138:628-44. 2009
    ..Here, we discuss recent insights into the importing and sorting of mitochondrial proteins and their contributions to mitochondrial biogenesis...
  64. pmc The human mitochondrial transcriptome
    Tim R Mercer
    Institute for Molecular Bioscience, The University of Queensland, Brisbane QLD 4072, Australia
    Cell 146:645-58. 2011
    ..previously undescribed transcripts, including small RNAs, and observe the enrichment of several nuclear RNAs in mitochondria. Using high-throughput in vivo DNaseI footprinting, we establish the global profile of DNA-binding protein ..
  65. ncbi Mitochondria, oxidative stress and cell death
    Martin Ott
    Institute of Environmental Medicine, Karolinska Institutet, S 171 77 Stockholm, Sweden
    Apoptosis 12:913-22. 2007
    In addition to the well-established role of the mitochondria in energy metabolism, regulation of cell death has recently emerged as a second major function of these organelles...
  66. doi PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1
    Sven Geisler
    Laboratory of Functional Neurogenetics, Otfried Muller Strasse 27, 72076 Tubingen, Germany
    Nat Cell Biol 12:119-31. 2010
    ..localization sequence are prerequisites to induce translocation of the E3 ligase Parkin to depolarized mitochondria. Subsequently, Parkin mediates the formation of two distinct poly-ubiquitin chains, linked through Lys 63 and ..
  67. ncbi Predicting subcellular localization of proteins based on their N-terminal amino acid sequence
    O Emanuelsson
    Stockholm Bioinformatics Center, Department of Biochemistry, Stockholm University, Stockholm, S 106 91, Sweden
    J Mol Biol 300:1005-16. 2000
    ..TargetP is available as a web-server at http://www.cbs.dtu.dk/services/TargetP/...
  68. pmc Bcl-x(L) retrotranslocates Bax from the mitochondria into the cytosol
    Frank Edlich
    Surgical Neurology Branch, NINDS, National Institutes of Health, Bethesda, MD 20892, USA
    Cell 145:104-16. 2011
    The Bcl-2 family member Bax translocates from the cytosol to mitochondria, where it oligomerizes and permeabilizes the mitochondrial outer membrane to promote apoptosis...
  69. pmc Animal mitochondrial genomes
    J L Boore
    Department of Biology, University of Michigan, 830 North University Avenue, Ann Arbor, MI 48109 1048, USA
    Nucleic Acids Res 27:1767-80. 1999
    ..The products of these genes, along with RNAs and proteins imported from the cytoplasm, endow mitochondria with their own systems for DNA replication, transcription, mRNA processing and translation of proteins...
  70. pmc Broad activation of the ubiquitin-proteasome system by Parkin is critical for mitophagy
    Nickie C Chan
    Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    Hum Mol Genet 20:1726-37. 2011
    Parkin, an E3 ubiquitin ligase implicated in Parkinson's disease, promotes degradation of dysfunctional mitochondria by autophagy...
  71. pmc Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia
    Huafeng Zhang
    Vascular Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    J Biol Chem 283:10892-903. 2008
    ....
  72. ncbi Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death
    Christopher P Baines
    Department of Pediatrics, Children s Hospital Medical Center, Cincinnati, Ohio 45229, USA
    Nature 434:658-62. 2005
    b>Mitochondria play a critical role in mediating both apoptotic and necrotic cell death. The mitochondrial permeability transition (mPT) leads to mitochondrial swelling, outer membrane rupture and the release of apoptotic mediators...
  73. doi Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase
    Christian Frezza
    Cancer Research UK, Beatson Institute for Cancer Research, Switchback Road, Glasgow G61 1BD, UK
    Nature 477:225-8. 2011
    ....
  74. ncbi p53 has a direct apoptogenic role at the mitochondria
    Motohiro Mihara
    Department of Pathology, Stony Brook University, Stony Brook, NY 11794, USA
    Mol Cell 11:577-90. 2003
    ..We recently reported that a fraction of induced p53 translocates to the mitochondria of apoptosing tumor cells. Targeting p53 to mitochondria is sufficient to launch apoptosis...
  75. pmc Circulating mitochondrial DAMPs cause inflammatory responses to injury
    Qin Zhang
    Department of Surgery, Division of Trauma, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
    Nature 464:104-7. 2010
    ..b>Mitochondria are evolutionary endosymbionts that were derived from bacteria and so might bear bacterial molecular motifs...
  76. ncbi BH3 domains of BH3-only proteins differentially regulate Bax-mediated mitochondrial membrane permeabilization both directly and indirectly
    Tomomi Kuwana
    La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92121, USA
    Mol Cell 17:525-35. 2005
    ..Bax directly and were the only BH3 peptides tested that could potently induce cytochrome c release from mitochondria in cultured cells...
  77. pmc During autophagy mitochondria elongate, are spared from degradation and sustain cell viability
    Ligia C Gomes
    Dulbecco Telethon Institute, Via Orus 2, 35129 Padova, Italy
    Nat Cell Biol 13:589-98. 2011
    ..The role of mitochondria and of their morphology during autophagy, a bulk degradation and recycling process of eukaryotic cells' ..
  78. pmc Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization
    Shireen A Sarraf
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nature 496:372-6. 2013
    ..These studies provide a resource for understanding how the PINK1-PARKIN pathway re-sculpts the proteome to support mitochondrial homeostasis...
  79. pmc Mitochondria and cancer
    Douglas C Wallace
    Children s Hospital of Philadelphia, Center for Mitochondrial and Epigenomic Medicine, Philadelphia, Pennsylvania 19104, USA
    Nat Rev Cancer 12:685-98. 2012
    Contrary to conventional wisdom, functional mitochondria are essential for the cancer cell...
  80. pmc Selective degradation of mitochondria by mitophagy
    Insil Kim
    Center for Cell Death, Injury and Regeneration, Departments of Pharmaceutical Sciences and Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA
    Arch Biochem Biophys 462:245-53. 2007
    b>Mitochondria are the essential site of aerobic energy production in eukaryotic cells. Reactive oxygen species (ROS) are an inevitable by-product of mitochondrial metabolism and can cause mitochondrial DNA mutations and dysfunction...
  81. pmc PINK1 is selectively stabilized on impaired mitochondria to activate Parkin
    Derek P Narendra
    Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
    PLoS Biol 8:e1000298. 2010
    ..Parkin is selectively recruited from the cytosol to damaged mitochondria to trigger their autophagy. How Parkin recognizes damaged mitochondria, however, is unknown...
  82. pmc Atg32 is a mitochondrial protein that confers selectivity during mitophagy
    Tomotake Kanki
    Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA
    Dev Cell 17:98-109. 2009
    ..We designated this autophagy-related (ATG) gene as ATG32. The Atg32 protein localizes on mitochondria. Following the induction of mitophagy, Atg32 binds Atg11, an adaptor protein for selective types of autophagy, ..
  83. pmc PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility
    Xinnan Wang
    F M Kirby Neurobiology Center, Children s Hospital Boston, Boston, MA 02115, USA
    Cell 147:893-906. 2011
    ..By preventing mitochondrial movement, the PINK1/Parkin pathway may quarantine damaged mitochondria prior to their clearance...
  84. ncbi PUMA, a novel proapoptotic gene, is induced by p53
    K Nakano
    Regulation of Cell Growth Laboratory, National Cancer Institute at Frederick, Maryland 21702, USA
    Mol Cell 7:683-94. 2001
    ..PUMA-alpha and PUMA-beta show similar activities; they bind to Bcl-2, localize to the mitochondria to induce cytochrome c release, and activate the rapid induction of programmed cell death...
  85. doi How increased oxidative stress promotes longevity and metabolic health: The concept of mitochondrial hormesis (mitohormesis)
    Michael Ristow
    Dept of Human Nutrition, Institute of Nutrition, University of Jena, Germany
    Exp Gerontol 45:410-8. 2010
    ..of aging (FRTA), these effects may be due to increased formation of reactive oxygen species (ROS) within the mitochondria causing an adaptive response that culminates in subsequently increased stress resistance assumed to ultimately ..
  86. pmc SIRT3 is a mitochondria-localized tumor suppressor required for maintenance of mitochondrial integrity and metabolism during stress
    Hyun Seok Kim
    Genetics of Development and Disease Branch, NIDDK, NIH, Bethesda, MD 20892, USA
    Cancer Cell 17:41-52. 2010
    ..Finally, human breast and other human cancer specimens exhibit reduced SIRT3 levels. These results identify SIRT3 as a genomically expressed, mitochondria-localized tumor suppressor.
  87. pmc Mitofusin 1 and mitofusin 2 are ubiquitinated in a PINK1/parkin-dependent manner upon induction of mitophagy
    Matthew E Gegg
    Department of Clinical Neurosciences, Institute of Neurology, University College London, London, UK
    Hum Mol Genet 19:4861-70. 2010
    ..Mutations in the Parkin and PINK1 genes are a cause of familial PD. PINK1 is a putative kinase associated with mitochondria, and loss of PINK1 expression leads to mitochondrial dysfunction, which increases with time...
  88. pmc Loss of PINK1 function promotes mitophagy through effects on oxidative stress and mitochondrial fission
    Ruben K Dagda
    Department of Pathology and Center for Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    J Biol Chem 284:13843-55. 2009
    ..without affecting oxidative stress, suggesting active involvement of autophagy in morphologic remodeling of mitochondria for clearance...
  89. doi Mitochondria-anchored receptor Atg32 mediates degradation of mitochondria via selective autophagy
    Koji Okamoto
    Division of Molecular Cell Biology, National Institute for Basic Biology, Okazaki, Japan
    Dev Cell 17:87-97. 2009
    b>Mitochondria are essential organelles that produce most of the energy for a cell, but concomitantly accumulate oxidative damage...
  90. pmc Autophagy suppresses tumorigenesis through elimination of p62
    Robin Mathew
    University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA
    Cell 137:1062-75. 2009
    ..tumor cells preferentially accumulated p62/SQSTM1 (p62), endoplasmic reticulum (ER) chaperones, damaged mitochondria, reactive oxygen species (ROS), and genome damage...
  91. pmc PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria
    Yun Chen
    Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    Science 340:471-5. 2013
    Senescent and damaged mitochondria undergo selective mitophagic elimination through mechanisms requiring two Parkinson's disease factors, the mitochondrial kinase PINK1 (PTEN-induced putative kinase protein 1; PTEN is phosphatase and ..
  92. ncbi Mitochondrial free radical generation, oxidative stress, and aging
    E Cadenas
    Department of Molecular Pharmacology and Toxicology, School of Pharmacy University of Southern California, Los Angeles 90033, USA
    Free Radic Biol Med 29:222-30. 2000
    b>Mitochondria have been described as "the powerhouses of the cell" because they link the energy-releasing activities of electron transport and proton pumping with the energy conserving process of oxidative phosphorylation, to harness the ..
  93. ncbi Endosymbiotic gene transfer: organelle genomes forge eukaryotic chromosomes
    Jeremy N Timmis
    School of Molecular and Biomedical Science, The University of Adelaide, South Australia 5005, Australia
    Nat Rev Genet 5:123-35. 2004
  94. pmc The PINK1/Parkin pathway regulates mitochondrial morphology
    Angela C Poole
    Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 105:1638-43. 2008
    ..integrity is currently unknown, although mutations in the PINK1 and parkin genes result in enlarged or swollen mitochondria, suggesting a possible regulatory role for the PINK1/Parkin pathway in mitochondrial morphology...
  95. ncbi Mediation of poly(ADP-ribose) polymerase-1-dependent cell death by apoptosis-inducing factor
    Seong Woon Yu
    Department of Neurology and Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
    Science 297:259-63. 2002
    ..We show that PARP-1 activation is required for translocation of apoptosis-inducing factor (AIF) from the mitochondria to the nucleus and that AIF is necessary for PARP-1-dependent cell death...
  96. doi Mitochondria and reactive oxygen species
    Alicia J Kowaltowski
    Departamento de Bioquimica, Instituto de Quimica, Universidade de Sao Paulo, Sao Paulo, Brazil
    Free Radic Biol Med 47:333-43. 2009
    b>Mitochondria are a quantitatively relevant source of reactive oxygen species (ROS) in the majority of cell types...
  97. pmc c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism
    Ping Gao
    Division of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Nature 458:762-5. 2009
    ..The unique means by which Myc regulates glutaminase uncovers a previously unsuspected link between Myc regulation of miRNAs, glutamine metabolism, and energy and reactive oxygen species homeostasis...
  98. pmc A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine
    Douglas C Wallace
    Center for Molecular and Mitochondrial Medicine and Genetics, Department of Ecology and Evolutionary Biology, University of California, Irvine, California 92697 3940, USA
    Annu Rev Genet 39:359-407. 2005
    ..Since the mitochondria use oxidative phosphorylation (OXPHOS) to convert dietary calories into usable energy, generating reactive ..
  99. ncbi Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration
    Libin Cui
    Department of Neurology, Massachusetts General Hospital, Harvard Medical School, MassGeneral Institute for Neurodegeneration, Charlestown, MA 02129 USA
    Cell 127:59-69. 2006
    ..These studies suggest a key role for PGC-1alpha in the control of energy metabolism in the early stages of HD pathogenesis...
  100. ncbi Mitochondria: more than just a powerhouse
    Heidi M McBride
    University of Ottawa Heart Institute, Canada
    Curr Biol 16:R551-60. 2006
    Pioneering biochemical studies have long forged the concept that the mitochondria are the 'energy powerhouse of the cell'...
  101. pmc Early deficits in synaptic mitochondria in an Alzheimer's disease mouse model
    Heng Du
    Department of Surgery, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    Proc Natl Acad Sci U S A 107:18670-5. 2010
    ..Thus, synaptic mitochondria are vital for maintenance of synaptic function and transmission through normal mitochondrial energy metabolism, ..

Research Grants69

  1. Mitochondrial Protection Within Chronically Ischemic Myocardium
    Edward O McFalls; Fiscal Year: 2010
    ..we will test the hypothesis that expression of uncoupling protein (UCP)-2, as an adaptive process within mitochondria from hibernating and preconditioned heart tissue in the "Second Window of Protection" (SWOP), is protective ..
  2. Air Pollution on Adiposity and Vascular Dysfunction: White or Brown Matters?
    Qinghua Sun; Fiscal Year: 2013
    ..microPET-CT) to evaluate the activity of brown adipose tissue, tissue histological examination to assess mitochondria content, adipocyte hyperplasia and hypertrophy, and vascular growth in the fat tissues, myograph to investigate ..
  3. Novel Mitochondrial Mechanisms of Ethanol-Induced Cardiac Injury in Aged Females
    DONNA HOPE KORZICK; Fiscal Year: 2010
    ..Because of the pivotal role played by the mitochondria in the maintenance of cell survival and cardioprotection, it is logical that ethanol and age-associated ..
  4. Role of Txnip in adapting fuel metabolism to nutritional state
    SIMON HUI; Fiscal Year: 2013
    ..ROS defense system will be measured as well as the levels of oxidative modified proteins, DNA and lipids in the mitochondria. To show the causative link between NADPH levels and mitochondrial function, NADPH levels in TKO embryonic ..
  5. Roles of Nitric Oxide and Superoxide in Cystitis
    ANTHONY JOHN KANAI; Fiscal Year: 2013
    ..This leads to swelling and rupture of the mitochondria, cytochrome c release and apoptosis. We developed a mitochondrial targeting strategy (U.S...
  6. THE ROLE OF ACETYLATION IN MITOCHONDRIAL FUNCTION
    Gary Cecchini; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Mitochondria generate much of the energy used by animal cells and are essential for cellular function...
  7. Functional Genomics of the Mitochondrial Proteome
    Dennis R Winge; Fiscal Year: 2011
    DESCRIPTION (provided by applicant): Mitochondria are essential organelles for cellular metabolism and survival...
  8. Collagen X and heparan sulfate proteoglycan in the hematopoietic stem cell niche.
    ELIZABETH G SWEENEY; Fiscal Year: 2012
    ..investigation include skeletogenesis, hematopoiesis, transgenesis and spermatogonial transplanation, cloning, mitochondria, pattern formation, chromatin structure, angiogenesis, arginylation as a posttranslational modification, ..
  9. Vascular dysfunction and oxidative stress in primary amyloidosis
    RAYMOND QUEZON MIGRINO; Fiscal Year: 2010
    ..This was associated with increased superoxide production. Mitochondria targeted antioxidant treatment preserved endothelial function. We will expand on our initial observations...
  10. Mitochondrial dysfunction, oxidative stress, and surgical acute kidney injury
    FREDERIC TREMAINE BILLINGS; Fiscal Year: 2013
    ..plasma and urine concentrations of F2-isoprostanes and isofurans, markers of mitochondrial function (mitochondria redox potential, peroxisome proliferator-activated receptor [unreadable] coactivator 1-[unreadable] (PGC-1[..
  11. Combination drug treatment to inhibit multiple cell death pathways after TBI
    ALAN IRA FADEN; Fiscal Year: 2010
    ..through the release of poly ADP ribose (PAR), is a critical upstream activator AIF release from neuronal mitochondria;it also more recently has been shown to be a critical activator of microglia...
  12. Protein Nitration in the Placenta
    Leslie Myatt; Fiscal Year: 2012
    ..At higher concentrations NO forms peroxynitrite which damages mitochondria causing release of cytochrome c and apoptosis...
  13. REGULATION OF PULMONARY CIRCULATION IN FETUS AND NEWBORN
    Girija G Konduri; Fiscal Year: 2013
    ..O2 availability and oxidative phosphorylation at birth may lead to increased reactive oxygen species (ROS) in mitochondria. However, the contribution of mitochondrial ROS to oxidative stress in PPHN is unknown...
  14. Pathogenesis of the Metabolic Syndrome
    W Timothy Garvey; Fiscal Year: 2013
    ..In addition, mitochondria isolated from muscle will be functionally studied for substrate oxidation capacity using high resolution ..
  15. Role of Mitochondria in the Regulation of Iron metabolism by Alcohol
    DUYGU DEE DEE HARRISON-FINDIK; Fiscal Year: 2012
    b>Mitochondria are critical in iron metabolism and play a role in alcohol-induced liver injury. Alcohol alters mitochondrial function and leads to oxidative stress...
  16. Mechanism-Based Discovery of Protectants Against Iron-Dependant Oxidative Injury
    JUSTIN M SCHWARTZ; Fiscal Year: 2011
    ..b>Mitochondria then take up this iron via the electrogenic calcium uniporter to promote intramitochondrial OH7 formation, the ..
  17. Surgical amelioration of type 2 diabetes: Hormones, microbiota and mitochondria
    PETER J contact HAVEL; Fiscal Year: 2010
    ..function (oxygen uptake, ROS production, mitochondrial coupling, and calcium transport) will be evaluated in mitochondria isolated from several tissues (liver, skeletal muscle, heart, and adipose)...
  18. Arsenic Trioxide and Acute Myeloid Leukemia
    Yongkui Jing; Fiscal Year: 2012
    ..Membrane localized NADPH oxidase and mitochondria are the main sources of ROS production...
  19. Genetic Studies of Optic Atrophy
    Taosheng Huang; Fiscal Year: 2012
    ..PUBLIC HEALTH RELEVANCE: Optic atrophy gene 1 (OPA1) programs proteins found in mitochondria, the power plant of cells in our body...
  20. Complex I: Role of L Subunit in Proton Translocation
    Steven B Vik; Fiscal Year: 2011
    ..Complex I (NADH:quinone oxidoreductase) is the entry point of NADH into the electron transport chain of mitochondria. It oxidizes NADH to NAD+ which allows the citric acid cycle to oxidize carbon compounds...
  21. Air Pollution on Adiposity and Vascular Dysfunction: White or Brown Matters?
    Qinghua Sun; Fiscal Year: 2010
    ..microPET-CT) to evaluate the activity of brown adipose tissue, tissue histological examination to assess mitochondria content, adipocyte hyperplasia and hypertrophy, and vascular growth in the fat tissues, intravital microscopy ..
  22. Cellular and Animal Models of FUS Mutations in ALS
    Eric J Huang; Fiscal Year: 2013
    ..are associated with markedly disorganized intracellular organelles, including endoplasmic reticulum (ER) and mitochondria. These results lead us to hypothesize that mutant FUS proteins dominantly inhibit normal RNA and protein ..
  23. New therapeutics for the treatment of Acinetobactor baumannii infections.
    ALLEN BERNARD REITZ; Fiscal Year: 2013
    ..There are marked differences between the components of the bacterial OxPhos with those of mitochondria and low sequence homology between the two, suggesting that pathogen-specific therapy by this approach is ..
  24. Impaired mitochondrial fusion in pulmonary arterial hypertension
    Stephen L Archer; Fiscal Year: 2010
    ..Normally, mitochondria rapidly join and break apart through highly regulated processes called fusion and fission, respectively...
  25. Metabolic regulation of diabetic nephropathy
    Karen Block; Fiscal Year: 2013
    ..Preliminary and published data generated in our laboratory demonstrate a novel localization of Nox4 to the mitochondria and enhanced NAD(P)H- dependent ROS generation within this compartment when cultured renal cells are exposed to ..
  26. MEMBRANES OF THE DENTAL PATHOGEN STREPTOCOCCUS MUTANS
    L Jeannine Brady; Fiscal Year: 2013
    ..In other prokaryotic and eukaryotic cells, as well as mitochondria, the same enzyme works in reverse as an ATP synthase...
  27. Ca Signaling in Progression of Amyotrophic Lateral Sclerosis in Skeletal Muscle
    Jingsong Zhou; Fiscal Year: 2013
    ..SOD1) gene are linked to most cases of inherited ALS, resulting in impaired metabolic function of the mitochondria. Currently, there is a lack of knowledge on how dysfunctional mitochondria and altered Ca signaling contribute ..
  28. Mechanistic Studies on Prostate Cancer Prevention by Gugulipid
    Dong Xiao; Fiscal Year: 2013
    ..the GL-mediated apoptosis in human prostate cancer cells is dependent on ROS;and furthermore, whether the mitochondria-derived ROS serve to initiate such GL-induced cell death. 2...
  29. The PKCepsilon-regulated oncogenic and tumor suppressor roles of ATF2 in melanoma
    ERIC KIRK LAU; Fiscal Year: 2013
    ..Thi phosphorylation blocks the ability of ATF2 to translocate to the mitochondria during genotoxic stress...
  30. Enhancing radiation and cisplatin HNSCC cell killing by inhibiting mitochondrial
    Lynn Harrison; Fiscal Year: 2013
    ..Damage to the mitochondrial genome can result in loss of functional mitochondria, an induction of oxidative stress and greater nuclear DNA damage...
  31. Structural biology of enzymes in fatty acid metabolism
    Liang Tong; Fiscal Year: 2012
    ..The carnitine palmitoyltransferases (CPTs) have crucial roles in the ?-oxidation of fatty acids in the mitochondria, and the malonyl-CoA product of ACC2 is a potent inhibitor of the CPT-I enzymes...
  32. Lifespan Extension Despite Greatly Elevated Insulin and Body Fat
    David E Harrison; Fiscal Year: 2013
    ..Collaborators will test free radical damage to proteins of the electron transport chains for liver and muscle mitochondria. Aim 3...
  33. Respiration in Sepsis
    Claude A Piantadosi; Fiscal Year: 2013
    ..also induces mitochondrial damage by loss of NO signal specificity and indiscriminate chemical attack on mitochondria by NO species (NOx)...
  34. Targeting GRK2 (BARK1) in Heart Failure
    Walter J Koch; Fiscal Year: 2013
    ..In addition, GRK2 can be found in/on mitochondria in cardiac myocytes through novel protein-protein interaction via the amino-terminus of GRK2...
  35. Novel Diagnostics to Detect Lung Injury
    Elizabeth R Jacobs; Fiscal Year: 2013
    ..Our preliminary data support a critical role for mitochondria in a rat model unilateral lung IR injury, a model of lung transplant which eliminates immunological or drug ..
  36. Role of estrogen-related receptors in cardiac and skeletal muscle
    Janice M Huss; Fiscal Year: 2010
    ..The capacity for mitochondria! ATP generation and the selection of energy substrates in heart and skeletal muscle is regulated by ..
  37. Mitochondrial Mechanisms of Programmed Necrosis in the Aged Female Heart
    Alexandra M Machikas; Fiscal Year: 2013
    ..In this regard, mitochondria have been targeted as mediators of apoptosis, autophagy and necrosis...
  38. Characterization of an essential mitochondrial rRNA methyltransferase
    Kip E Guja; Fiscal Year: 2013
    ..factor B1 (TFB1M) is essential for mammalian development and catalyzes the analogous rRNA modification in mitochondria. Methylation by KsgA is related to bacterial aminoglycoside sensitivity and TFB1M activity could similarly be ..
  39. Nanoelectrode arrays for study of the molecular mechanisms, triggers, and inhibit
    Peter J Burke; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Mitochondria are the central regulator of apoptosis, a process initiated by the activation of the mitochondrial permeability transition pore (mtPTP), an aggregate of several mitochondrial proteins...
  40. Metabolic Dysfunction and Neuroprotection after Pediatric Head Injury
    Susanna Scafidi; Fiscal Year: 2013
    ..enzymes impairment, which precludes pyruvate, generated via glycolysis, from being utilized in the mitochondria for energy production. In addition to glucose, the developing brain can utilize alternative substrates, i.e...
  41. Nitric Oxide in Pulmonary Hypertension
    Serpil C Erzurum; Fiscal Year: 2013
    ..In association with low NO, the cells have reduced mitochondria numbers &respiration, which is accompanied by ~3-fold increase in glycolysis for energy production...
  42. Cooperative Multicenter Reproductive Medicine Network (U10)
    MARCELLE IVONNE CEDARS; Fiscal Year: 2013
    ..damage to mtDNA and enzymes involved in coQ10 synthesis would reduce the substrate for ATP production by the mitochondria. We hypothesize that altered mitochondrial function in oocytes reflects diminished availability of coQ10 with ..
  43. FASEB SRC on Mitochondrial Assembly &Dynamics in Health, Disease &Aging
    Antoni Barrientos; Fiscal Year: 2011
    ..In addition, the role of mitochondria in general neurodegenerative diseases such as Parkinson's and during the aging process will be discussed ..
  44. Mitochondrial Oxidative Stress in the Retinal Pigment Epithelium as a Model for A
    Alfred S Lewin; Fiscal Year: 2013
    ..One source of the RPE- damaging reactive oxygen species (ROS) are the mitochondria of the RPE cells themselves...
  45. Glutathione in mitochondrial dysfunction and disease progression in ALS-models
    Marcelo R Vargas; Fiscal Year: 2011
    ..Malfunction of the mitochondria, the powerhouse of the cell, may be responsible for the observed neurodegeneration...
  46. Surgical Revascularization's Impact on Mitochondria in Hibernating Myocardium
    ROSEMARY FRANCES KELLY; Fiscal Year: 2013
    ..state of the revascularized myocardium to the hibernating myocardium, quantifying the proteomic changes in the mitochondria of both groups and evaluating enzymatic protein activity as directed by the proteomic changes...
  47. Deacetylation of mitochondrial proteins protect neurons from ischemic injury
    Conrad Alano; Fiscal Year: 2013
    ..Of the known sirtuins (or Sirts), three are localized within the mitochondria (Sirt3, -4, and -5)...
  48. Role of SIRT3 in fetal programming and kidney dysfunction
    Karen R Jonscher; Fiscal Year: 2013
    ..biochemist interested in elucidating the mechanism of action of pyrroloquinoline quinone (PQQ) in cells and mitochondria;advisor Dr...
  49. Visualization of ototoxic mitochondrial dysfunction in mammalian hair cells
    Shelley A Batts; Fiscal Year: 2012
    ..b>Mitochondria have been well-established to be the "powerhouse" of the cell by generating most of cells'ATP, but these ..
  50. TRP channels in regulation of vascular tone
    David X Zhang; Fiscal Year: 2013
    ..serves as a common mechanism for the release of two otherwise diversely regulated relaxing factors (NO and mitochondria-derived H2O2) responsible for FMD in the human coronary microcirculation...
  51. Sphingosine 1-phosphate and cardioprotection
    JOEL SAMUEL KARLINER; Fiscal Year: 2012
    ..studies, we showed that S1P1 receptor function, Akt activation, and cell substrates interacting with mitochondria contribute to S1P prosurvival effects...
  52. Nuclear Control of Mitochondrial Gene Expression
    Gerald Shadel; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Mitochondria are multi-faceted organelles in eukaryotic cells that stand at the nexus of energy metabolism, oxidative stress, and apoptosis...
  53. Mechanisms and metabolic implications of LRP130 in NAFLD
    Marcus P Cooper; Fiscal Year: 2013
    ..In NAFLD, defective mitochondria liberate excess reactive oxygen species (ROS)...
  54. Reperfusion and Neurovascular Injury in Stroke
    Pak H Chan; Fiscal Year: 2013
    ..We have demonstrated that cerebral ischemia and reperfusion increase superoxide radicals in brain mitochondria, which leads to metalloproteinase-9 (MMP-9) activation and BBB disruption that characterize neurovascular ..
  55. Molecular Regulation of Ischemic Renal Failure
    Zheng Dong; Fiscal Year: 2013
    ..We have further revealed a striking morphological change of mitochondria during tubular cell apoptosis, i.e. mitochondrial fragmentation...
  56. Investigating the pathogenesis of CoQ10 deficiencies
    Catarina M Quinzii; Fiscal Year: 2013
    ..NARRATIVE: Defects of mitochondria cause diverse human diseases...
  57. C. Elegans and Mitochondrial K+ Channels
    KEITH W NEHRKE; Fiscal Year: 2013
    ..b>Mitochondria are central to the pathogenesis of ischemia- perfusion injury and are believed to be a major target for ..
  58. SIRT1 as a regulator of health and lifespan of mammals
    David A Sinclair; Fiscal Year: 2013
    ..reduced respiration and ATP, increased reactive oxygen species (ROS) and lactate, and a failure of muscle mitochondria to adapt their metabolism to fasting. Strikingly, this same defect occurs in wild type mice as they age...
  59. Pathogenesis of Oxidative Stress in Chagas Disease
    Nisha Jain Garg; Fiscal Year: 2013
    ..in the idea that the interaction of parasite (antioxidants) and host (PARP-1/Nrf1/2) molecules via abundant mitochondria in the cardiomyocytes is the key event resulting in chronic evolution of chagasic cardiomyopathy...
  60. AAA ATPases linking mitochondria with microtubule processing in flies and yeast
    Karen G Hales; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Mitochondria, the organelles in which food energy is harnessed into usable ATP form, are moved and shaped to fulfill different energy needs within specialized cells...
  61. Role of Mitochondria Targeted CYP2E1 and HO-1 in Alcohol Mediated Tissue Injury
    Narayan G Avadhani; Fiscal Year: 2012
    ..P4502E1 (CYP2E1) and inducible heme oxygenase 1 (HO-1) and a number of other proteins are bimodally targeted to mitochondria in addition to their well-established ER or cytoplasmic destination...
  62. INTRACELLULAR CALCIUM IN HAIR CELLS
    Robert Fettiplace; Fiscal Year: 2013
    ..The contributions of Ca2+ buffering and uptake into intracellular compartments, especially the mitochondria, to limit Ca2+ transients will be studied...
  63. A Targeted Preemptive Approach to Addressing Mitochondrial Toxicity of Nucleoside
    John K Buolamwini; Fiscal Year: 2013
    ..NRTI triphosphates, the metabolites that inhibit Pol g can be synthesized inside mitochondria from imported NRTIs from the cytosol...
  64. Molecular Genetics of Caloric Restriction in Aging Flies
    Blanka Rogina; Fiscal Year: 2013
    ..Considering the crucial role of mitochondria in energy production and cellular homeostasis, our preliminary data provide additional links between metabolic ..
  65. Alteration of ER:mitochondrial contacts by human cytomegalovirus infection
    ANAMARIS MARTHA COLBERG POLEY; Fiscal Year: 2010
    ..synthesis, UL37 proteins are translocated into the endoplasmic reticulum (ER) membrane and then imported into mitochondria, where they have potent anti- apoptotic functions...
  66. Mitochondrial SOD & Breast Cancer Risk-Mechanism
    JAMES YAGER; Fiscal Year: 2003
    ..The protein encoded by the Val allele exhibited decreased import in isolated rat liver mitochondria. Furthermore, Val homozygotes had an increased risk of nonfamilial cardiomyopathy in Japanese patients...
  67. Diaphragm Mitochondrial Alterations in Sepsis
    Leigh Callahan; Fiscal Year: 2004
    DESCRIPTION (Applicant's abstract): Recent work suggests that mitochondria dysfunction plays a central role in sepsis, a major cause of death and morbidity in the United States...
  68. INCREASED MEMBRANE POTENTIAL IN CARCINOMA MITOCHONDRIA
    JOSEPHINE MODICA NAPOLITANO; Fiscal Year: 1999
    ..The proposed study involves a comprehensive, comparative biochemical and molecular analysis of mitochondria isolated from several control and carcinoma cell lines that display differences in mitochondrial membrane ..
  69. Retrograde Signaling in Alcohol-Induced Mitochondrial Stress and Biogenesis.
    Neil Kaplowitz; Fiscal Year: 2009
    ..g., Hsp60 and 10) and mitochondrial biogenesis in response to stress to mitochondria (e.g., protein malfolding or oxidative modifications) as would occur from alcohol...