mitochondrial diseases

Summary

Summary: Diseases caused by abnormal function of the MITOCHONDRIA. They may be caused by mutations, acquired or inherited, in mitochondrial DNA or in nuclear genes that code for mitochondrial components. They may also be the result of acquired mitochondria dysfunction due to adverse effects of drugs, infections, or other environmental causes.

Top Publications

  1. ncbi Mitochondrial respiratory-chain diseases
    Salvatore DiMauro
    Department of Neurology, Columbia University College of Physicians and Surgeons, New York, USA
    N Engl J Med 348:2656-68. 2003
  2. ncbi The role of mitochondrial dysfunction in psychiatric disease
    Fernando Scaglia
    Department of Molecular and Human Genetics, Baylor College of Medicine and Texas Children s Hospital, 6621 Fannin, Houston, TX 77030, USA
    Dev Disabil Res Rev 16:136-43. 2010
  3. pmc Human mitochondrial DNA: roles of inherited and somatic mutations
    Eric A Schon
    Department of Neurology, Columbia University Medical Center, 630 West 168th Street, New York, New York 10032, USA
    Nat Rev Genet 13:878-90. 2012
  4. pmc Mitochondrial DNA mutations in human disease
    Robert W Taylor
    Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, The Medical School, University of Newcastle upon Tyne, NE2 4HH, United Kingdom
    Nat Rev Genet 6:389-402. 2005
  5. pmc High-throughput, pooled sequencing identifies mutations in NUBPL and FOXRED1 in human complex I deficiency
    Sarah E Calvo
    Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA
    Nat Genet 42:851-8. 2010
  6. pmc Pathogenic mitochondrial DNA mutations are common in the general population
    Hannah R Elliott
    Mitochondrial Research Group, Newcastle University, Newcastle upon Tyne, UK
    Am J Hum Genet 83:254-60. 2008
  7. ncbi Mitochondrial phenylalanyl-tRNA synthetase mutations underlie fatal infantile Alpers encephalopathy
    Jenni M Elo
    Research Programs Unit, Molecular Neurology, Biomedicum Helsinki, University of Helsinki, 00290 Helsinki, Finland
    Hum Mol Genet 21:4521-9. 2012
  8. ncbi Prevalence of mitochondrial DNA disease in adults
    Andrew M Schaefer
    Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, Newcastle University, Newcastle upon Tyne, United Kingdom
    Ann Neurol 63:35-9. 2008
  9. ncbi Mitochondrial diseases
    Anthony H V Schapira
    Department of Clinical Neurosciences, Institute of Neurology, University College London, London, UK
    Lancet 379:1825-34. 2012
  10. ncbi Mitochondrial aspartyl-tRNA synthetase deficiency causes leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation
    Gert C Scheper
    Department of Pediatrics and Child Neurology, Vrije University Medical Center, 1081 HV Amsterdam, The Netherlands
    Nat Genet 39:534-9. 2007

Detail Information

Publications322 found, 100 shown here

  1. ncbi Mitochondrial respiratory-chain diseases
    Salvatore DiMauro
    Department of Neurology, Columbia University College of Physicians and Surgeons, New York, USA
    N Engl J Med 348:2656-68. 2003
  2. ncbi The role of mitochondrial dysfunction in psychiatric disease
    Fernando Scaglia
    Department of Molecular and Human Genetics, Baylor College of Medicine and Texas Children s Hospital, 6621 Fannin, Houston, TX 77030, USA
    Dev Disabil Res Rev 16:136-43. 2010
    ....
  3. pmc Human mitochondrial DNA: roles of inherited and somatic mutations
    Eric A Schon
    Department of Neurology, Columbia University Medical Center, 630 West 168th Street, New York, New York 10032, USA
    Nat Rev Genet 13:878-90. 2012
    ..Here we discuss insights into the roles of mtDNA mutations in a wide variety of diseases, highlighting the interesting genetic characteristics of the mitochondrial genome and challenges in studying its contribution to pathogenesis...
  4. pmc Mitochondrial DNA mutations in human disease
    Robert W Taylor
    Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, The Medical School, University of Newcastle upon Tyne, NE2 4HH, United Kingdom
    Nat Rev Genet 6:389-402. 2005
    ..However, many challenges remain, including the prevention and treatment of these diseases. This review explores the advances that have been made and the areas in which future progress is likely...
  5. pmc High-throughput, pooled sequencing identifies mutations in NUBPL and FOXRED1 in human complex I deficiency
    Sarah E Calvo
    Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA
    Nat Genet 42:851-8. 2010
    ..Our study illustrates how large-scale sequencing, coupled with functional prediction and experimental validation, can be used to identify causal mutations in individual cases...
  6. pmc Pathogenic mitochondrial DNA mutations are common in the general population
    Hannah R Elliott
    Mitochondrial Research Group, Newcastle University, Newcastle upon Tyne, UK
    Am J Hum Genet 83:254-60. 2008
    ..The exclusive detection of m.14484T-->C on haplogroup J implicates the background mtDNA haplotype in mutagenesis. These findings emphasize the importance of developing new approaches to prevent transmission...
  7. ncbi Mitochondrial phenylalanyl-tRNA synthetase mutations underlie fatal infantile Alpers encephalopathy
    Jenni M Elo
    Research Programs Unit, Molecular Neurology, Biomedicum Helsinki, University of Helsinki, 00290 Helsinki, Finland
    Hum Mol Genet 21:4521-9. 2012
    ..This study establishes a new genetic cause of infantile mitochondrial Alpers encephalopathy and reports a new mitochondrial aminoacyl-tRNA synthetase as a cause of mitochondrial disease...
  8. ncbi Prevalence of mitochondrial DNA disease in adults
    Andrew M Schaefer
    Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, Newcastle University, Newcastle upon Tyne, United Kingdom
    Ann Neurol 63:35-9. 2008
    ..Consequently, the aim of this study was to accurately define the prevalence of mtDNA disease (primary mutation occurs in mtDNA) in the working-age population of the North East of England...
  9. ncbi Mitochondrial diseases
    Anthony H V Schapira
    Department of Clinical Neurosciences, Institute of Neurology, University College London, London, UK
    Lancet 379:1825-34. 2012
    ..Inherited mitochondrial diseases can be caused by mutations of mitochondrial DNA or of nuclear genes that encode mitochondrial proteins...
  10. ncbi Mitochondrial aspartyl-tRNA synthetase deficiency causes leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation
    Gert C Scheper
    Department of Pediatrics and Child Neurology, Vrije University Medical Center, 1081 HV Amsterdam, The Netherlands
    Nat Genet 39:534-9. 2007
    ..Enzyme activities of mutant proteins were decreased. We were surprised to find that activities of mitochondrial complexes from fibroblasts and lymphoblasts derived from affected individuals were normal, as determined by different assays...
  11. ncbi Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion
    Alice Bourdon
    Institut National de la Sante et de la Recherche Médicale U781 and Service de Génétique, Hopital Necker Enfants Malades, 149 rue de Sevres, 75015 Paris, France
    Nat Genet 39:776-80. 2007
    ..Accordingly, severe mtDNA depletion was found in various tissues of the Rrm2b-/- mouse. The mtDNA depletion triggered by p53R2 alterations in both human and mouse implies that p53R2 has a crucial role in dNTP supply for mtDNA synthesis...
  12. ncbi Mitochondrial function in normal and diabetic beta-cells
    P Maechler
    Division of Clinical Biochemistry, Department of Internal Medicine, University Medical Centre, 1211 Geneva 4, Switzerland
    Nature 414:807-12. 2001
    ..The latter process requires an increase in cytosolic Ca2+, which depends on ATP synthesized by the mitochondria. This organelle also generates other factors, of which glutamate has been proposed as a potential intracellular messenger...
  13. ncbi Mitochondrial diseases of the brain
    Rajnish K Chaturvedi
    CSIR Indian Institute of Toxicology Research, 80 MG Marg, Lucknow 226001, India
    Free Radic Biol Med 63:1-29. 2013
    ..We also discuss clinical trials of bioenergetics agents in neurodegenerative disorders. Lastly, we shed light on PGC-1α, TORC-1, AMP kinase, Nrf2-ARE, and Sirtuins as novel therapeutic targets for neurodegenerative disorders. ..
  14. pmc Defects in mitochondrial DNA replication and human disease
    William C Copeland
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Durham, North Carolina 27709, USA
    Crit Rev Biochem Mol Biol 47:64-74. 2012
    ..This review focuses on our current knowledge of genetic defects of mtDNA replication (POLG, POLG2, C10orf2) and nucleotide metabolism (TYMP, TK2, DGOUK, and RRM2B) that cause instability of mtDNA and mitochondrial disease...
  15. ncbi Targeting antioxidants to mitochondria by conjugation to lipophilic cations
    Michael P Murphy
    MRC Dunn Human Nutrition Unit, Wellcome Trust MRC Building, Cambridge CB2 2XY, United Kingdom
    Annu Rev Pharmacol Toxicol 47:629-56. 2007
    ..Here we review the background and work to date on this class of mitochondria-targeted antioxidants...
  16. ncbi Mechanisms of mitochondrial diseases
    Emil Ylikallio
    Research Programs Unit, Molecular Neurology, Biomedicum Helsinki, University of Helsinki, Finland
    Ann Med 44:41-59. 2012
    ..The mitochondrial diseases are defined by impairment of OXPHOS...
  17. pmc Amyloid-beta overproduction causes abnormal mitochondrial dynamics via differential modulation of mitochondrial fission/fusion proteins
    Xinglong Wang
    Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA
    Proc Natl Acad Sci U S A 105:19318-23. 2008
    ....
  18. pmc Exome sequencing identifies mitochondrial alanyl-tRNA synthetase mutations in infantile mitochondrial cardiomyopathy
    Alexandra Götz
    Research Programs Unit, Molecular Neurology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
    Am J Hum Genet 88:635-42. 2011
    ..Furthermore, we show that mitochondrial disorders extend to prenatal life and are an important cause of early infantile cardiac failure...
  19. pmc Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production
    Aleksandra Trifunovic
    Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden
    Proc Natl Acad Sci U S A 102:17993-8. 2005
    ..We propose instead that respiratory chain dysfunction per se is the primary inducer of premature aging in mtDNA mutator mice...
  20. pmc Mitochondrial dysfunction in the elderly: possible role in insulin resistance
    Kitt Falk Petersen
    Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
    Science 300:1140-2. 2003
    ..These data support the hypothesis that an age-associated decline in mitochondrial function contributes to insulin resistance in the elderly...
  21. ncbi The mitochondrial proteome and human disease
    Sarah E Calvo
    Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA
    Annu Rev Genomics Hum Genet 11:25-44. 2010
    ..Finally, we explore future prospects and challenges for using the mitochondrial proteome as a foundation for systems analysis of the organelle...
  22. pmc Mitochondrial dysfunction and pathology in bipolar disorder and schizophrenia
    Hayley B Clay
    Neuroscience Graduate Program, Vanderbilt University, Nashville, TN 37232, USA
    Int J Dev Neurosci 29:311-24. 2011
    ..Understanding the role of mitochondria, both developmentally as well as in the ailing brain, is of critical importance to elucidate pathophysiological mechanisms in psychiatric disorders...
  23. ncbi Oxidative stress and mitochondrial dysfunction in neurodegenerative diseases
    E Trushina
    Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
    Neuroscience 145:1233-48. 2007
    ..In this review, while focusing on Huntington's disease (HD), we discuss similarities among HD, Friedreich ataxia and xeroderma pigmentosum, which provide insight into shared mechanisms of neuronal death...
  24. ncbi Mammalian mitochondrial complex I: biogenesis, regulation, and reactive oxygen species generation
    Werner J H Koopman
    Department of Biochemistry, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Antioxid Redox Signal 12:1431-70. 2010
    ....
  25. ncbi Mitochondrial DNA mutations in human disease
    S DiMauro
    College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    Am J Med Genet 106:18-26. 2001
    ..We review recent progress in prenatal diagnosis, epidemiology, and in the development of animal models harboring mtDNA mutations...
  26. pmc Cerebellar ataxia in patients with mitochondrial DNA disease: a molecular clinicopathological study
    Nichola Zoe Lax
    Mitochondrial Research Group, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, United Kingdom
    J Neuropathol Exp Neurol 71:148-61. 2012
    ..These findings highlight the vulnerability of the olivary-cerebellum to mtDNA defects...
  27. ncbi Genomic analysis of mitochondrial diseases in a consanguineous population reveals novel candidate disease genes
    Hanan E Shamseldin
    Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
    J Med Genet 49:234-41. 2012
    ..To investigate the utility of autozygome analysis and exome sequencing in a cohort of patients with suspected or confirmed mitochondrial encephalomyopathy...
  28. pmc Epigenetics, epidemiology and mitochondrial DNA diseases
    Patrick F Chinnery
    Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK
    Int J Epidemiol 41:177-87. 2012
    ..These observations open the door to future studies investigating the role of mtDNA methylation in human disease...
  29. pmc Towards germline gene therapy of inherited mitochondrial diseases
    Masahito Tachibana
    Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health and Science University, 505 NW 185th Avenue, Beaverton, Oregon 97006, USA
    Nature 493:627-31. 2013
    ..The mtDNA can be efficiently replaced in human oocytes. Although some ST oocytes displayed abnormal fertilization, remaining embryos were capable of developing to blastocysts and producing embryonic stem cells similar to controls...
  30. ncbi Mitochondrial DNA mutations and human disease
    Helen A L Tuppen
    Mitochondrial Research Group, Institute for Ageing and Health, The Medical School, Newcastle University, Newcastle upon Tyne NE24HH, UK
    Biochim Biophys Acta 1797:113-28. 2010
    ..The functional consequences of mtDNA mutations that have been characterised to date will also be discussed, along with current and potential future diagnostic and therapeutic advances...
  31. pmc Nuclear factors involved in mitochondrial translation cause a subgroup of combined respiratory chain deficiency
    John P Kemp
    Mitochondrial Research Group, Institute of Human Genetics, Newcastle University, Central Parkway, Newcastle upon Tyne NE1 3BZ, UK
    Brain 134:183-95. 2011
    ....
  32. ncbi Treatment for mitochondrial disorders
    Gerald Pfeffer
    Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK
    Cochrane Database Syst Rev 4:CD004426. 2012
    ..This major update was carried out to identify new studies and grade the original studies for potential bias in accordance with revised Cochrane Collaboration guidelines...
  33. ncbi Minimum birth prevalence of mitochondrial respiratory chain disorders in children
    Daniela Skladal
    The Murdoch Children s Research Institute, Royal Children s Hospital, Parkville 3052, Melbourne, Australia
    Brain 126:1905-12. 2003
    ..Combining our data with a previous study on prevalence of adult-onset respiratory chain disorders predicts a minimum birth prevalence of 13.1/100 000 or 1/7634 for respiratory chain disorders with onset at any age...
  34. ncbi Mitochondria: dynamic organelles in disease, aging, and development
    David C Chan
    Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA
    Cell 125:1241-52. 2006
    ..Clearly, much about the basic biology of mitochondria remains to be understood. Here we discuss recent work that suggests that the dynamics (fusion and fission) of these organelles is important in development and disease...
  35. ncbi Random point mutations with major effects on protein-coding genes are the driving force behind premature aging in mtDNA mutator mice
    Daniel Edgar
    Division of Metabolic Diseases, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
    Cell Metab 10:131-8. 2009
    ....
  36. ncbi A neurological perspective on mitochondrial disease
    Robert McFarland
    Mitochondrial Research Group, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK
    Lancet Neurol 9:829-40. 2010
    ..b>Mitochondrial diseases are among the most frequently inherited neurological disorders, and can be caused by mutations in ..
  37. ncbi Mitochondrial dysfunction in NASH: causes, consequences and possible means to prevent it
    Karima Begriche
    Institut National de la Santé et de la Recherche Médicale INSERM Unité 481, Faculte de Medecine Xavier Bichat, 16 rue Henri Huchard, 750118 Paris, France
    Mitochondrion 6:1-28. 2006
    ..Finding a drug, which could fully prevent oxidative stress and mitochondrial dysfunction in NASH is a major challenge for the next decade...
  38. ncbi The investigation and diagnosis of pathogenic mitochondrial DNA mutations in human urothelial cells
    John K Blackwood
    Mitochondrial Research Group, Institute for Ageing and Health, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
    Biochem Biophys Res Commun 393:740-5. 2010
    ..Our results have implications for the diagnosis, management and counselling of families with mtDNA disease...
  39. pmc Loss of PINK1 causes mitochondrial functional defects and increased sensitivity to oxidative stress
    Clement A Gautier
    Center for Neurologic Diseases, Brigham and Women s Hospital, Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 105:11364-9. 2008
    ....
  40. ncbi Assembly factors as a new class of disease genes for mitochondrial complex I deficiency: cause, pathology and treatment options
    Jessica Nouws
    Nijmegen Centre for Mitochondrial Disorders at the Department of Paediatrics, Radboud University Nijmegen Medical Centre, 6500 HB, Nijmegen, The Netherlands
    Brain 135:12-22. 2012
    ..In this review, we will address whether the functions of these chaperones point towards a general molecular mechanism of disease and whether this enables us to design a treatment for complex I deficiency...
  41. ncbi Mitochondria-specific RNA-modifying enzymes responsible for the biosynthesis of the wobble base in mitochondrial tRNAs. Implications for the molecular pathogenesis of human mitochondrial diseases
    Noriko Umeda
    Department of Chemistry and Biotechnology, Graduate School of Engineering, University of Tokyo, Japan
    J Biol Chem 280:1613-24. 2005
    ..Partial inactivation of MTU1 in HeLa cells by small interference RNA also reduced their oxygen consumption and resulted in mitochondria with defective membrane potentials, which are similar phenotypic features observed in MERRF...
  42. pmc Targeted exome sequencing of suspected mitochondrial disorders
    Daniel S Lieber
    Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA
    Neurology 80:1762-70. 2013
    ..To evaluate the utility of targeted exome sequencing for the molecular diagnosis of mitochondrial disorders, which exhibit marked phenotypic and genetic heterogeneity...
  43. ncbi Mitochondrial tRNA mutations and disease
    John W Yarham
    Mitochondrial Research Group, Institute for Ageing and Health, The Medical School, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK
    Wiley Interdiscip Rev RNA 1:304-24. 2010
    ....
  44. pmc Mitochondrial disorders caused by mutations in respiratory chain assembly factors
    Francisca Diaz
    Department of Neurology, University of Miami Miller School of Medicine, Miami, Florida, USA
    Semin Fetal Neonatal Med 16:197-204. 2011
    b>Mitochondrial diseases involve the dysfunction of the oxidative phosphorylation (OXPHOS) system. This group of diseases presents with heterogeneous clinical symptoms affecting mainly organs with high energy demands...
  45. ncbi Mitochondrial respiratory dysfunction-elicited oxidative stress and posttranslational protein modification in mitochondrial diseases
    Yu Ting Wu
    Department of Biochemistry and Molecular Biology, School of Life Sciences, National Yang Ming University, Taipei, Taiwan
    Ann N Y Acad Sci 1201:147-56. 2010
    Pathogenic mutation in mtDNA and mitochondrial dysfunction are associated with mitochondrial diseases. In this review, we discuss the oxidative stress-elicited mitochondrial protein modifications that may contribute to the pathophysiology ..
  46. ncbi Mitochondrial complex I deficiency: from organelle dysfunction to clinical disease
    Felix Distelmaier
    Department of Membrane Biochemistry, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Brain 132:833-42. 2009
    ....
  47. ncbi Mitochondrial complex I: structure, function and pathology
    Rolf J R J Janssen
    Nijmegen Centre for Mitochondrial Disorders, Laboratory of Paediatrics and Neurology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    J Inherit Metab Dis 29:499-515. 2006
    ..Unravelling the intricate mechanisms underlying the functioning of this membrane-bound enzyme complex in health and disease will pave the way for developing adequate diagnostic procedures and advanced therapeutic treatment strategies...
  48. ncbi Retinal ganglion cell neurodegeneration in mitochondrial inherited disorders
    Valerio Carelli
    Department of Neurological Sciences, University of Bologna, Via Ugo Foscolo 7, 40123, Bologna, Italy
    Biochim Biophys Acta 1787:518-28. 2009
    ....
  49. pmc An enhanced MITOMAP with a global mtDNA mutational phylogeny
    Eduardo Ruiz-Pesini
    Center for Molecular and Mitochondrial Medicine and Genetics MAMMAG and Departments of Biological Chemistry, Ecology and Evolutionary Biology, and Pediatrics, University of California, Irvine, CA 92697 3900, USA
    Nucleic Acids Res 35:D823-8. 2007
    ..These additions position MITOMAP for the implementation of our automated mtDNA sequence analysis system, Mitomaster...
  50. pmc Mitochondrial translation and beyond: processes implicated in combined oxidative phosphorylation deficiencies
    Paulien Smits
    Department of Pediatrics, Nijmegen Center for Mitochondrial Disorders, Radboud University Nijmegen Medical Center, Geert Grooteplein 10, P O Box 9101, 6500 HB Nijmegen, The Netherlands
    J Biomed Biotechnol 2010:737385. 2010
    ..This knowledge is important for further research into the genetic causes, with the ultimate goal to effectively prevent and cure these complex and often devastating disorders...
  51. ncbi Mammalian mitochondrial nucleoids: organizing an independently minded genome
    Ian J Holt
    MRC Dunn Human Nutrition Unit, Wellcome Trust MRC Building, Hills Road, Cambridge CB2 OXY, UK
    Mitochondrion 7:311-21. 2007
    ....
  52. ncbi Spectrophotometric assay for complex I of the respiratory chain in tissue samples and cultured fibroblasts
    Antoon J M Janssen
    Department of Pediatrics and Laboratory of Pediatrics and Neurology, The Nijmegen Centre for Mitochondrial Disorders at Radboud University Medical Centre, Nijmegen, The Netherlands
    Clin Chem 53:729-34. 2007
    ..This deficiency is mainly due to the poor solubility of coenzyme-Q analogs and reaction mixture turbidity caused by the relatively high concentrations of tissue extract that are often required to measure complex I...
  53. ncbi Mitochondrial disease: a practical approach for primary care physicians
    Richard H Haas
    Department of Neurosciences, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093 0935, USA
    Pediatrics 120:1326-33. 2007
    ....
  54. pmc Simultaneous detection and quantification of mitochondrial DNA deletion(s), depletion, and over-replication in patients with mitochondrial disease
    Ren Kui Bai
    Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, NAB 2015, Houston, TX 77030, USA
    J Mol Diagn 7:613-22. 2005
    ..demonstrate that both qualitative and quantitative analyses are important in molecular diagnosis of mitochondrial diseases. The presence of deletion(s) and mtDNA depletion or compensatory over-replication can be determined ..
  55. pmc Mitochondrial energetics and therapeutics
    Douglas C Wallace
    Center for Molecular and Mitochondrial Medicine and Genetics and Departments of Biological Chemistry, Ecology and Evolutionary Biology, and Pediatrics, University of California at Irvine, Irvine, California 92697 3940, USA
    Annu Rev Pathol 5:297-348. 2010
    ....
  56. ncbi Mitochondrial dysfunction in neurodegenerative diseases and cancer
    Michelle Barbi de Moura
    Department of Pharmacology and Chemical Biology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA
    Environ Mol Mutagen 51:391-405. 2010
    ..This article reviews how dysfunctional mitochondria contribute to Alzheimer's disease, Parkinson's disease, Huntington's disease, and several human cancers...
  57. ncbi Mitochondrial disorders: prevalence, myths and advances
    D R Thorburn
    The Murdoch Children s Research Institute and Genetic Health Services Victoria, Royal Children s Hospital, and Department of Paediatrics, University of Melbourne, Melbourne, Australia
    J Inherit Metab Dis 27:349-62. 2004
    ..While a cautious approach is needed, there is now a consensus that prenatal diagnosis should be offered to some women, particularly those at lower recurrence risk. Preimplantation genetic diagnosis can also be an option...
  58. ncbi Mitochondrial dysfunction in autism spectrum disorders: a population-based study
    G Oliveira
    Outpatient Clinic of Autism, Centro de Desenvolvimento da Criança, Hospital Pediátrico de Coimbra, 3000 076 Coimbra, Portugal
    Dev Med Child Neurol 47:185-9. 2005
    ..2%) and warranting further investigation...
  59. ncbi Human mitochondrial complex I assembly is mediated by NDUFAF1
    Rutger O Vogel
    Department of Paediatrics, Radboud University Nijmegen Medical Centre, Netherlands
    FEBS J 272:5317-26. 2005
    ..Based on these data, we propose that NDUFAF1 is an important protein for the assembly/stability of complex I...
  60. ncbi The mitochondrial transporter family (SLC25): physiological and pathological implications
    Ferdinando Palmieri
    Department of Pharmaco Biology, Laboratory of Biochemistry and Molecular Biology, University of Bari, Via Orabona 4, 70125, Bari, Italy
    Pflugers Arch 447:689-709. 2004
    ..It is likely that further extension and functional characterization of the SLC25 gene family will elucidate other diseases caused by MC deficiency...
  61. ncbi Reactive oxygen species and mitochondrial diseases
    I G Kirkinezos
    Department of Cell Biology and Anatomy, University of Miami School of Medicine, 1095 NW 14th Terrace, Miami, FL 33136, USA
    Semin Cell Dev Biol 12:449-57. 2001
    ..Here, we review the molecular mechanisms of ROS production and damage, as well as the existing evidence of mitochondrial ROS involvement in human diseases...
  62. ncbi Cardiomyopathy in children with mitochondrial disease; clinical course and cardiological findings
    D Holmgren
    Division of Pediatric Cardiology, The Queen Silvia Children s Hospital, Goteborg, Sweden
    Eur Heart J 24:280-8. 2003
    ..To determine the frequency of cardiomyopathy in children with mitochondrial disease and describe their clinical course, prognosis and cardiological manifestations...
  63. ncbi Clinical spectrum, morbidity, and mortality in 113 pediatric patients with mitochondrial disease
    Fernando Scaglia
    Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
    Pediatrics 114:925-31. 2004
    ..The aim of this study was to elucidate the frequency of major clinical manifestations in children with mitochondrial disease and establish their clinical course, prognosis, and rates of survival depending on their clinical features...
  64. pmc The in-depth evaluation of suspected mitochondrial disease
    Richard H Haas
    Department of Neurosciences, University of California San Diego, La Jolla, CA and Rady Children s Hospital San Diego, San Diego, CA, United States
    Mol Genet Metab 94:16-37. 2008
    ..The aim of this work is to facilitate the diagnosis of mitochondrial disease by geneticists, neurologists, and other metabolic specialists who face the challenge of evaluating patients of all ages with suspected mitochondrial disease...
  65. ncbi Phenotypic spectrum associated with mutations of the mitochondrial polymerase gamma gene
    Rita Horvath
    Metabolic Diseases Centre, Munich Schwabing, Institutes of Clinical Chemistry, Molecular Diagnostics and Mitochondrial Genetics, Academic Hospital Schwabing Munich, Germany
    Brain 129:1674-84. 2006
    ..1399G-->A (A467T) is common in children, but complete POLG1 sequencing is required to identify multiple mutations that can have complex implications for genetic counselling...
  66. pmc Manipulating the metazoan mitochondrial genome with targeted restriction enzymes
    Hong Xu
    Department of Biochemistry and Biophysics, University of California at San Francisco, San Francisco, CA 94158 2200, USA
    Science 321:575-7. 2008
    ..Thus, germline expression of mitochondrial restriction enzymes creates a powerful selection and has allowed direct isolation of mitochondrial mutants in a metazoan...
  67. ncbi Pharmacologic effects on mitochondrial function
    Bruce H Cohen
    Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, 9500 Euclid Avenue, Cleveland, OH 44195, USA
    Dev Disabil Res Rev 16:189-99. 2010
    ..It is hoped that preclinical pharmacogenetic and functional studies of mitochondrial toxicity, along with personalized genomic medicine, will improve both our understanding of mitochondrial drug toxicity and patient safety...
  68. ncbi Development and implementation of standardized respiratory chain spectrophotometric assays for clinical diagnosis
    F Medja
    INSERM, U975, Paris F 75013, France
    Mitochondrion 9:331-9. 2009
    ..The French network of mitochondrial diseases diagnostic centers undertook comparison of the results obtained with different protocols in the French ..
  69. ncbi Plasma thiol status is altered in children with mitochondrial diseases
    Heli Salmi
    University of Helsinki, Hospital for Children and Adolescents, Helsinki, Finland
    Scand J Clin Lab Invest 72:152-7. 2012
    ..Better understanding of the pathogenesis of mitochondrial diseases is important in order to improve their treatment.
  70. ncbi Next-generation sequencing for mitochondrial diseases: a wide diagnostic spectrum
    Valeria Vasta
    University of Washington School of Medicine, Seattle Children s Research Institute, C9S, 1900 9th Avenue, Seattle, WA 98101, USA
    Pediatr Int 54:585-601. 2012
    ..Clinical sequencing tests are available only for a limited number of genes. Recently, massively parallel sequencing has become a powerful tool for testing genetically heterogeneous conditions such as mitochondrial disorders...
  71. ncbi Acute liver failure with subsequent cirrhosis as the primary manifestation of TRMU mutations
    Ulrike Schara
    Pediatric Neurology, University of Essen, Essen, Germany
    J Inherit Metab Dis 34:197-201. 2011
    ..We suggest that TRMU deficiency should be considered in infants with acute liver disease...
  72. ncbi Gene therapy for mitochondrial disease by delivering restriction endonuclease SmaI into mitochondria
    Masashi Tanaka
    Department of Gene Therapy, Gifu International Institute of Biotechnology, Mitake, Japan
    J Biomed Sci 9:534-41. 2002
    ..Delivery of restriction enzymes into mitochondria is a novel strategy for gene therapy of a special form of mitochondrial diseases.
  73. pmc A proposed consensus panel of organisms for determining evolutionary conservation of mt-tRNA point mutations
    John W Yarham
    Mitochondrial Research Group, Institute for Ageing and Health, The Medical School, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK
    Mitochondrion 12:533-8. 2012
    ....
  74. ncbi Mitochondrial disease and epilepsy
    Shamima Rahman
    Mitochondrial Research Group, Clinical and Molecular Genetics Unit, UCL Institute of Child Health, University College London, 30 Guilford Street, London, UK
    Dev Med Child Neurol 54:397-406. 2012
    ..b>Mitochondrial diseases are genetically heterogeneous; to date, mutations have been reported in all 37 mitochondrially encoded ..
  75. pmc NDUFS4: creation of a mouse model mimicking a Complex I disorder
    Christopher A Ingraham
    Department of Biomedical Genetics, Univ of Rochester Medical Center, Rochester, NY, USA
    Mitochondrion 9:204-10. 2009
    ..Decreased Complex I activity with unaltered Complex II activity, along with an accumulation of lactate, were consistent with Complex I disorders in this mouse model...
  76. ncbi POLG1-related and other "mitochondrial Parkinsonisms": an overview
    Daniele Orsucci
    Department of Neuroscience, Neurological Clinic, University of Pisa, Via Roma 67, 56126 Pisa, Italy
    J Mol Neurosci 44:17-24. 2011
    ..Lastly, we try to introduce a possible diagnostic approach for patients with parkinsonism and suspected mitochondrial disorder...
  77. ncbi Mitochondrial DNA mutations and ageing
    Laura C Greaves
    Mitochondrial Research Group, Institute for Ageing and Health, The Medical School, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK
    Biochim Biophys Acta 1790:1015-20. 2009
    ..Here we review the current literature, and discuss the evidence for and against a causal role of mtDNA mutations in ageing and in the pathogenesis of age-related disease...
  78. pmc A mutation in C2orf64 causes impaired cytochrome c oxidase assembly and mitochondrial cardiomyopathy
    Merei Huigsloot
    Nijmegen Center for Mitochondrial Disorders, Department of Pediatrics, Radboud University Nijmegen Medical Centre, PO Box 9101, NL 6500HB, Nijmegen, The Netherlands
    Am J Hum Genet 88:488-93. 2011
    ....
  79. ncbi The psychiatric manifestations of mitochondrial disorders: a case and review of the literature
    Rebecca E Anglin
    Department of Psychiatry, McMaster University, Hamilton, Ontario, Canada
    J Clin Psychiatry 73:506-12. 2012
    ..To date, this issue has received little attention in the literature, and mitochondrial disorders are likely underdiagnosed in psychiatric patients...
  80. ncbi MELAS and L-arginine therapy: pathophysiology of stroke-like episodes
    Yasutoshi Koga
    Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Fukuoka, Japan
    Ann N Y Acad Sci 1201:104-10. 2010
    ..Currently, L-arginine therapy may be the most promising for the treatment of stroke-like episodes in MELAS...
  81. ncbi Is Alzheimer's disease a disorder of mitochondria-associated membranes?
    Eric A Schon
    Department of Neurology, Columbia University Medical Center, New York, NY, USA
    J Alzheimers Dis 20:S281-92. 2010
    ....
  82. ncbi Localized cerebral energy failure in DNA polymerase gamma-associated encephalopathy syndromes
    Charalampos Tzoulis
    Department of Neurology, Haukeland University Hospital, 5021 Bergen, Norway
    Brain 133:1428-37. 2010
    ..We suggest therefore that both infantile and later onset polymerase gamma related encephalopathies are part of a continuum...
  83. ncbi Causes of death in pedigrees with the 3243A>G mutation in mitochondrial DNA
    K Majamaa-Voltti
    Department of Internal Medicine, University of Oulu, P O Box 5000, FIN 90014 Oulu, Finland
    J Neurol Neurosurg Psychiatry 79:209-11. 2008
    ..Causes of death of patients with the 3243A>G mutation have been described in case reports or case series with a limited number of subjects...
  84. ncbi Transmitochondrial mice as models for mitochondrial DNA-based diseases
    Kazuto Nakada
    Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305 8572, Japan
    Exp Anim 60:421-31. 2011
    ..resultant mitochondrial respiratory abnormalities are associated with a wide variety of disorders, such as mitochondrial diseases, neurodegenerative diseases, diabetes, and cancer, as well as aging...
  85. ncbi Exome sequencing identifies MRPL3 mutation in mitochondrial cardiomyopathy
    Louise Galmiche
    Department of Genetics, INSERM U781, Hopital Necker Enfants Malades, Universite Paris Descartes, Paris, France
    Hum Mutat 32:1225-31. 2011
    ..This observation gives support to the view that exome sequencing combined with genetic mapping is a powerful approach for the identification of new genes of mitochondrial disorders...
  86. pmc Mutations in the ND5 subunit of complex I of the mitochondrial DNA are a frequent cause of oxidative phosphorylation disease
    M J Blok
    Department of Clinical Genetics, University Hospital, Maastricht, The Netherlands
    J Med Genet 44:e74. 2007
    ..However, mutations in other mtDNA regions can be an important cause of oxidative phosphorylation (OXPHOS) disease as well...
  87. ncbi The implications of mitochondrial DNA copy number regulation during embryogenesis
    Phillippa J Carling
    Mitochondrial Research Group, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK
    Mitochondrion 11:686-92. 2011
    ..Here we review current understanding of the factors regulating the amount of mtDNA within cells and discuss the relevance of these findings to our understanding of the inheritance of mtDNA heteroplasmy...
  88. pmc A fatal mitochondrial disease is associated with defective NFU1 function in the maturation of a subset of mitochondrial Fe-S proteins
    Aleix Navarro-Sastre
    Division of Inborn Errors of Metabolism, Department of Biochemistry and Molecular Genetics, Hospital Clinic, Instituto de Investigación Biomédica Pi Sunyer, 08028 Barcelona, Spain
    Am J Hum Genet 89:656-67. 2011
    ..Importantly, yeast Nfu1 protein carrying the individuals' missense mutation was functionally impaired. We conclude that NFU1 functions as a late-acting maturation factor for a subset of mitochondrial Fe-S proteins...
  89. pmc Energy metabolism affects susceptibility of Anopheles gambiae mosquitoes to Plasmodium infection
    Jose Henrique M Oliveira
    Laboratório de Bioquímica de Artrópodes Hematófagos, Instituto de Bioquimica Medica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
    Insect Biochem Mol Biol 41:349-55. 2011
    ..We conclude that there are broad metabolic differences between R and S An. gambiae mosquitoes that influence their susceptibility to Plasmodium infection...
  90. ncbi Ageing muscle: clonal expansions of mitochondrial DNA point mutations and deletions cause focal impairment of mitochondrial function
    Guillemette Fayet
    INSERM U523, Institut de Myologie, Hopital Pitie Salpetriere, Paris, France
    Neuromuscul Disord 12:484-93. 2002
    ..Their focal accumulation causes significant impairment of mitochondrial function in individual cells in spite of low overall levels of mitochondrial DNA mutations in muscle...
  91. ncbi Diagnostic criteria for respiratory chain disorders in adults and children
    F P Bernier
    Murdoch Childrens Research Institute, Royal Children s Hospital, Flemington Road, Parkville VIC 3052, Australia
    Neurology 59:1406-11. 2002
    ..Respiratory chain (RC) disorders are clinically, biochemically, and molecularly heterogeneous. The lack of standardized diagnostic criteria poses difficulties in evaluating diagnostic methodologies...
  92. ncbi Autistic disorder in 2 children with mitochondrial disorders
    Chang Yong Tsao
    Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA
    J Child Neurol 22:1121-3. 2007
    ....
  93. ncbi Mitochondrial diseases and the role of the yeast models
    Teresa Rinaldi
    Department of Cell and Developmental Biology, Pasteur Institute Cenci Bolognetti Foundation, Sapienza University of Rome, Rome, Italy
    FEMS Yeast Res 10:1006-22. 2010
    Nowadays, mitochondrial diseases are recognized and studied with much attention and they cannot be considered anymore as 'rare diseases'...
  94. ncbi Hereditary optic neuropathies share a common mitochondrial coupling defect
    Arnaud Chevrollier
    Institut National de la Sante et de la Recherche Medicale, U694, Départment de Biochimie et Génétique, Centre Hospitalier Universitaire, Angers, France
    Ann Neurol 63:794-8. 2008
    ..Interestingly, the energetic defect was significantly more pronounced in Leber's hereditary optic neuropathy and autosomal dominant optic atrophy patients with a more complex phenotype, the so-called plus phenotype...
  95. ncbi Mitochondrial disorders
    Massimo Zeviani
    Division of Molecular Neurogenetics, Istituto Nazionale Neurologico C Besta, Via Celoria 11 20133 Milan, Italy
    Brain 127:2153-72. 2004
    ..This review describes human genetic diseases associated with mtDNA and nuclear DNA mutations leading to impaired OXPHOS...
  96. pmc Biochemical diagnosis of mitochondrial disorders
    Richard J T Rodenburg
    Nijmegen Center for Mitochondrial Disorders NCMD, 656 Department of Pediatrics, Department of Laboratory Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
    J Inherit Metab Dis 34:283-92. 2011
    ....
  97. ncbi The deoxyguanosine kinase gene is mutated in individuals with depleted hepatocerebral mitochondrial DNA
    H Mandel
    Metabolic Disease Unit, Department of Pediatrics, Rambam Medical Center, Technion Israel Institute of Technology, Bruce Rappaport Faculty of Medicine, Haifa, Israel
    Nat Genet 29:337-41. 2001
    ..The association of mtDNA depletion with mutated DGUOK suggests that the salvage-pathway enzymes are involved in the maintenance of balanced mitochondrial dNTP pools...
  98. ncbi Multiple oxidative phosphorylation deficiencies in severe childhood multi-system disorders due to polymerase gamma (POLG1) mutations
    Maaike C de Vries
    Nijmegen Centre for Mitochondrial Disorders, Departments of Pediatrics, Laboratory of Pediatrics and Neurology and Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Eur J Pediatr 166:229-34. 2007
    ..Conclusion We suggest performing POLG1 mutation analysis in children with combined oxidative phosphorylation deficiencies in muscle, even if the clinical picture is not Alpers syndrome...
  99. pmc Secondary mitochondrial dysfunction in propionic aciduria: a pathogenic role for endogenous mitochondrial toxins
    Marina A Schwab
    Department of General Pediatrics, Division of Inborn Metabolic Diseases, University Children s Hospital Heidelberg, Im Neuenheimer Feld 150, D 69120 Heidelberg, Germany
    Biochem J 398:107-12. 2006
    ....
  100. pmc Gene expression in a Drosophila model of mitochondrial disease
    Daniel J M Fernández-Ayala
    Institute of Medical Technology and Tampere University Hospital, University of Tampere, Tampere, Finland
    PLoS ONE 5:e8549. 2010
    ....
  101. ncbi Mitochondrial respiratory chain super-complex I-III in physiology and pathology
    Giorgio Lenaz
    Dipartimento di Biochimica, Universita di Bologna, Via Irnerio 48, 40126 Bologna, Italy
    Biochim Biophys Acta 1797:633-40. 2010
    ..There is increasing evidence that disruption of the super-complex organization leads to functional derangements responsible for pathological changes, as we have found in K-ras-transformed fibroblasts...

Research Grants70

  1. MITDNA MUTAGENESIS BY ENVIRONMENTAL CARCINOGENS
    Keshav Singh; Fiscal Year: 2003
    ..past decade it has been clearly recognized that mutations in mitDNA lead to pathogenesis of a variety of mitochondrial diseases. It is estimated that of the 4 million children born each year in the United States, up to 4,000 develop ..
  2. Characterization of an essential mitochondrial rRNA methyltransferase
    Kip E Guja; Fiscal Year: 2013
    ..The goal of this proposal is to provide a more complete understanding of how TFB proteins influence disease pathogenesis by elucidating the roles that they play in mitochondrial gene expression. ..
  3. FASEB SRC on Mitochondrial Assembly &Dynamics in Health, Disease &Aging
    Antoni Barrientos; Fiscal Year: 2011
    ..b>Mitochondrial diseases that will be discussed include rare inherited diseases such as Leber's Hereditary Optic Neuropathy (..
  4. SIRT1 as a regulator of health and lifespan of mammals
    David A Sinclair; Fiscal Year: 2013
    ..By understanding how the two genomes communicate -- between each other and potentially to other cells in the body -- the study could lead to new practical strategies for combating rare mitochondrial diseases and common diseases of aging.
  5. Transport ATPases: From Molecules to Maladies
    Rajini Rao; Fiscal Year: 2010
    ..disease, immune and infectious diseases, ulcers, diabetes, vision and hearing loss, neurodegeneration and mitochondrial diseases. Sessions will include Rotary Catalysis, Structure and Mechanism of ATPases, Membrane Dynamics and Vesicle ..
  6. Kinetics of DNA polymerase gamma upon mutation and nucleoside analog exposure
    CHRISTAL DYANE SOHL; Fiscal Year: 2013
    ..DNA deletion or depletion resulting from deficient DNA pol 3 activity has been observed in many mitochondrial diseases which affect about 60,000 Americans (1), and in HIV which currently affects an estimated one million ..
  7. Mitochondrial Gene Therapy
    Shoukhrat M Mitalipov; Fiscal Year: 2013
    ..In this study, we will explore feasibility, efficiency and safety of this novel mitochondrial gene replacement therapy in a clinically relevant nonhuman primate model. ..
  8. Enzymology of RNA Processing
    Carol A Fierke; Fiscal Year: 2013
    ..therapeutics to characterization of the biological pathways linked to the pathogenesis of multiple mitochondrial diseases. This proposal consists of two primary objectives...
  9. Transgenic Mitomice Models for Treatment of Blinding Diseases
    John Guy; Fiscal Year: 2013
    ..Our motivation in pursuing this project is to develop gene therapy for untreatable mitochondrial diseases that lead to blindness...
  10. Detection of S-(2-succino)cysteine (2SC) as a Biomarker of Mitochondrial Disease
    Norma Frizzell; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Mitochondrial diseases occur at a rate of 1 in 5000 live births and are often fatal by ~5 years old...
  11. Physical and Functional Systems Analysis of Mammalian Mitochondria
    JODI M NUNNARI; Fiscal Year: 2013
    ..and assess for variation in putative posttranslational modification sites involved in the progression of mitochondrial diseases (Aim1)...
  12. Installation of Energy-Efficient Cage Washers for Childrens Hospital Vivarium
    Philip R Johnson; Fiscal Year: 2012
    ..cell disease, hemophilia, pediatric oncology, fetal stem-cell therapy, fetal lung growth, cystic fibrosis, mitochondrial diseases, asthma, epilepsy, infectious diseases, and vaccine development...
  13. CONTROL OF NEURONAL ORGANELLE TRANSPORT
    Peter J Hollenbeck; Fiscal Year: 2013
    ..In the third aim, we will use Drosophila models of human mitochondrial diseases to critically assess the hypothesis that the proximal cause of neuropathology in mitochondrial ..
  14. Discovery of Biomakers in Human Mitochondrial Disorders
    RONALD WAYNE DAVIS; Fiscal Year: 2011
    ..The identification of new mitochondrial disease genes with our cost-effective and high quality clinical resequencing approach has important implications to better understand the role of mitochondria in human health. ..
  15. Mitochondrial Functions of Dynamin-Related Proteins
    Alexander M van der Bliek; Fiscal Year: 2012
    ..will broaden our knowledge of mitochondrial fission and fusion, and provide new avenues for treatments of mitochondrial diseases. PUBLIC HEALTH RELEVANCE: Mitochondria are the power plants in cells...
  16. Metabolic regulation in growth factor-dependent cells
    Ralph J DeBerardinis; Fiscal Year: 2010
    ..Pediatric mitochondrial diseases are untreatable genetic disorders that disrupt metabolism of lipids and other substances...
  17. Dissecting the role of mitochondrial DNA mutations in cancer
    Sean David Taylor; Fiscal Year: 2013
    ..Mutations in mtDNA are responsible for several mitochondrial diseases, and are suspected to contribute to the etiology of other age-related disorders including ..
  18. Modulation of Oxidative phosphorylation by mitochondrial soluble adenylyl cyclase
    Giovanni Manfredi; Fiscal Year: 2013
    ..These mice recapitulate biochemical and clinical characteristics of mitochondrial diseases. We will assess how sAC-cAMP-PKA modulation and protein phosphorylation in mitochondria from affected ..
  19. Control of Neural Organelle Transport
    PETER HOLLENBECK; Fiscal Year: 2009
    ..In the third aim, we will use Drosophila models of human mitochondrial diseases to test the hypothesis that the proximal cause of neuropathology in mitochondrial neurodegenerative ..
  20. MOLECULAR REMEDY OF MITOCHONDRIAL DEFECTS
    Takao Yagi; Fiscal Year: 2013
    ..Complex I defects are involved in many human mitochondrial diseases. Leber's hereditary optic neuropathy (LHON) is recognized as the frequently occurring complex I ..
  21. Regulation of Substrate Binding and Catalysis in tRNase Z
    LOUIS F LEVINGER; Fiscal Year: 2010
    ..Mutations in tRNAs are associated with maternally transmitted mitochondrial diseases and syndromes...
  22. Structural Aspects of Protein Synthesis in the Mammalian Mitochondria
    Rajendra K Agrawal; Fiscal Year: 2013
    ..Furthermore, defects in mitochondrial translation are associated with several human mitochondrial diseases. The long-term goal of our study is to understand the mechanism of translation in mammalian mitochondria, ..
  23. Proton-Translocating Sector of E. coli H+ATP Synthase
    Robert H Fillingame; Fiscal Year: 2010
    ..focuses on the interactions of the "water stream and the wheel" and should provide insight into human mitochondrial diseases in which these interactions are defective, and to new classes of drugs/antibiotics that block rotation of ..
  24. Impaired amino acid metabolism in mitochondrial diseases
    Giovanni Manfredi; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Mitochondrial diseases are heterogeneous genetic disorders caused by respiratory chain (RC) impairment...
  25. BIOGENESIS OF THE MITOCHONDRIAL INNER MEMBRANE
    Carla M Koehler; Fiscal Year: 2013
    ..abstract_text> ..
  26. North American Mitochondrial Disease Consortium (NAMDC)
    JOHN L THOMPSON; Fiscal Year: 2013
    ..established a network of nine clinical centers to improve the diagnosis, natural history, and treatment of mitochondrial diseases due to defects of the respiratory chain (RC)...
  27. Mouse models for mitochondrial disorders caused by mtDNA mutations
    Mikhail F Alexeyev; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Mitochondrial diseases caused by mutations in the mitochondrial DNA (mtDNA) are an important source of morbidity and mortality, yet only supportive care is available to affected patients...
  28. MITOCHONDRIAL ENCEPHALOMYOPATHIES AND MENTAL RETARDATION
    Salvatore DiMauro; Fiscal Year: 2013
    ....
  29. ASSEMBLY OF MEMBRANES IN HEART AND YEAST MITOCHONDRIA
    ALEXANDER A TZAGOLOFF; Fiscal Year: 2013
    ..The studies described in this proposal will continue to improve the yeast model as it applies to human mitochondrial diseases. PUBLIC HEALTH RELEVANCE: Because of its experimental tractability, the unicellular yeast Saccharomyces ..
  30. Towards gene therapy of mitochondrial disease
    Michael D Koob; Fiscal Year: 2010
    ..approach for mouse models of FRDA and to work towards adapting these therapies to treating FRDA and other mitochondrial diseases in humans...
  31. NEUROBIOLOGY OF DISEASE IN CHILDREN CONFERENCES
    Bernard L Maria; Fiscal Year: 2013
    ..abstract_text> ..
  32. Proton pumping mechanism in complex I
    EIKO OGISO; Fiscal Year: 2013
    ..Thus CI dysfunction is implicated in a variety of mitochondrial diseases including heart failure, type 2 diabetes, and neurodegenerative diseases such as Parkinson's disease...
  33. ASSEMBLY OF MEMBRANES IN HEART AND YEAST MITOCHONDRIA
    Alexander Tzagoloff; Fiscal Year: 2009
    ..Further characterizations of the mutants in our collection will enlarge on this information and thereby improve the yeast model as it applies to human mitochondrial diseases.
  34. RNA Import into Mitochondria and Neurodegenerative Disorders
    Eriko Shimada; Fiscal Year: 2013
    ..significant because deciphering RNA import requirements may lead to applications in treating mitochondrial diseases by targeted import of corrective RNAs...
  35. Biosynthesis and Insertion of Heme A during Cytochrome c Oxidase Biogenesis
    Eric L Hegg; Fiscal Year: 2013
    ..The synergy provided by employing both systems positions us to make rapid progress addressing these essential questions of CcO biogenesis. ..
  36. CoEnzyme Q10 in Statin Myopathy
    PAUL DAVIS THOMPSON; Fiscal Year: 2010
    ....
  37. Mitochondrial generation of superoxide in male reproduction
    Baisong Lu; Fiscal Year: 2010
    ..Mitochondrial dysfunction is responsible fOf a wide variety of severe mitochondrial diseases. Impairment of mitoc:hondrial function is one of the factors thaI contribute to infertility...
  38. Mitophagy-driven selection against heteroplasmic mitochondrial DNA mutations
    David K Simon; Fiscal Year: 2012
    ....
  39. Regulation of Mitochondria by Exercise and PGC-1 Coactivators in Skeletal Muscle
    GLENN CAMERON ROWE; Fiscal Year: 2013
    ..Results from this proposal will serve as the foundation and preliminary data for an R series proposal such as an R01 within 3-5 years. ..
  40. A novel recessive genetic screen for mitochondrial phenotypes in mammalian cells
    WILLIAM JAMES CRAIGEN; Fiscal Year: 2011
    ..are rare, recent epidemiological evidence suggests that the minimal prevalence of respiratory chain mitochondrial diseases is 1 in 5000...
  41. 3D Structure of Membrane Proteins
    Michael Radermacher; Fiscal Year: 2013
    ..Defects in Complex I are the cause of many mitochondrial diseases, among them are myopathies, central nervous system disorders, Alzheimer's and Parkinson's ..
  42. 2013 Cellular and Molecular Mechanisms of Toxicity Gordon Research Conference and
    Jose E Manautou; Fiscal Year: 2013
    ..The Conference will feature a wide range of topics, such as mitochondrial diseases, epigenetics, nanotechnology, transcriptional control of drug metabolizing enzymes, carcinogenesis, stem ..
  43. BACTERIAL CYTOCHROME BC1: STRUCTURE, FUNCTION, BIOGENESIS
    M FEVZI DALDAL; Fiscal Year: 2013
    ..extremely harmful for human cells, and their biogenesis components form the molecular bases of many common mitochondrial diseases in humans...
  44. Study of redox regulated pathways in the mitochondrion
    DEEPA VINAY DABIR; Fiscal Year: 2010
    ..in development of potential treatments and therapies for deafness-dystonia syndrome and other devastating mitochondrial diseases. Additionally, import pathways should be better characterized because they might serve as delivery systems ..
  45. Manipulation and Transfection of Mitochondrial DNA
    OLIVER CALVIN LOSON; Fiscal Year: 2012
    ..Second, mitochondrial transfection would enable the development of cell and animal models for study of mitochondrial diseases. With the ability to create models of mitochondrial pathologies, therapeutics research would receive a ..
  46. Development of HTS assays for mitochondrial function
    Michael King; Fiscal Year: 2009
    ..These mitochondrial diseases display great diversity in clinical signs and symptoms and morphological and biochemical characteristics...
  47. Mitochondrial Transcription and Pediatric Disease
    NEAL J SONDHEIMER; Fiscal Year: 2013
    ..The proposal overall advances the goal of studying biochemical processes and metabolism as these relate to brain functioning, injury and long term consequences to the brain. ..
  48. The mammalian citochondrial code
    Ya Ming Hou; Fiscal Year: 2013
    ..The significance of the work is high in that it addresses at the fundamental level why mutations and lack of modification in mitochondrial tRNAs are associated with over 100 mitochondrial disorders. ..
  49. Mechanisms of Mitochondrial Myopathy
    Andres Hernandez; Fiscal Year: 2013
    ..The proposed project aims to elucidate causative mechanisms and to assist in the development of pharmacological treatment that could increase the quality of life of individuals with these diseases. ..
  50. DEVELOPING A NORTH AMERICAN MITOCHONDRIAL DISEASE CONSORTIUM (NAMDC)
    Russell P Saneto; Fiscal Year: 2010
    ..b>Mitochondrial diseases are among the most clinically heterogeneous conditions because mitochondria are ubiquitous organelles and ..
  51. ATPIF1 inhibition as a therapeutic strategy for mitochondrial dysfunction
    Walter W Chen; Fiscal Year: 2013
    ..It is our hope that the biological processes identified through such a screen may eventually serve as novel targets for inhibition via pharmacological methods or gene therapy. ..
  52. Defining the genetic basis of human respiratory chain disease
    VAMSI KRISHNA MOOTHA; Fiscal Year: 2010
    ..We will analyze the DNA of patients with such disorders to discover their molecular basis. The results of this study may help us better diagnose and treat these devastating diseases. ..
  53. Mitochondrial Biogenesis and Dynamics in Health, Disease and Aging
    Gerald Shadel; Fiscal Year: 2013
    ..The major topics that will be covered in this meeting are: 1) Basic Mitochondrial Biology, 2) Mitochondrial Diseases;3) Mitochondria in Aging and Longevity;4) New Frontiers in Mitochondrial Biology and Medicine...
  54. Elucidating mitochondrial pathomechanisms of ENT3 disorders in ENT3 KO mice
    Rajgopal Govindarajan; Fiscal Year: 2013
    ..The proposed research is innovative because it would enable applicability to multiple skin and musculoskeletal disorders. ..
  55. Hypoxic stabilization of OXPHOS complexes in mitochondrial defects
    Francisca Diaz; Fiscal Year: 2013
    ..Declines in the mitochondrial oxidative phosphorylation (OXPHOS) system are associated with bona fide mitochondrial diseases as well as with numerous neurodegenerative disorders (e.g...
  56. mtDNA heteroplasmy in development and differentiation: an in-vitro approach
    RAJ RAGHAVENDRA RAO; Fiscal Year: 2013
    ..abstract_text> ..
  57. PHASE 3 TRIAL OF COENZYME IN MITOCHONDRIAL DISEASE
    PETER WALLACE STACPOOLE; Fiscal Year: 2011
    Treatment of mitochondrial diseases has been generally disappointing and has usually been approached in an uncontrolled manner...
  58. Molecular prostheses for mitochondrial disorders
    VAMSI KRISHNA MOOTHA; Fiscal Year: 2013
    ..If successful, this project will yield an entire pipeline of small molecules and proteins that may represent the starting point for a new class of therapeutics for these disorders. ..
  59. SETTING THE STAGE FOR REPLACEMENT OF MITOCHONDRIAL GENES
    CARLOS TORRES MORAES; Fiscal Year: 2013
    ..We have obtained preliminary data showing that this approach is feasible and propose to better characterize the system in vitro, ex vivo and in vivo. ..
  60. Mitochondrial RNA transport as a novel therapy
    MICHAEL JOHN PALLADINO; Fiscal Year: 2013
    Project summary: Archetypical mitochondrial diseases are common and devastating conditions with an extremely poor prognosis. Gene therapies have been proposed including allotopic expression of recoded mitochondrial genes from the nucleus...
  61. Mitochondrial Assembly and Dynamics in Health and Disease
    Carla Koehler; Fiscal Year: 2009
    ..b>Mitochondrial diseases that will be discussed include rare inherited diseases such as Leber's Hereditary Optic Neuropathy (..
  62. FACSVantage SE Upgrade
    RAYMOND HESTER; Fiscal Year: 2004
    ....
  63. Mitochondrial dysfunction in HAART: Point of care tests
    Michael F Marusich; Fiscal Year: 2010
    ..The 1st generation OXPHOS dipstick tests are already being used in studies of inherited mitochondrial diseases, neurodegenerative disorders (PD and Friedreich s Ataxia), and other metabolic disorders such as sepsis ..
  64. Small molecule modulators for mitochondrial protein import
    Carla Koehler; Fiscal Year: 2009
    ..probes that we can translate to vertebrate systems to probe mitochondrial function, including the link to mitochondrial diseases, because protein import is highly conserved from yeast to mammals...
  65. FTIR Studies of Photosynthetic Oxygen Evolution
    RICHARD DEBUS; Fiscal Year: 2009
    ..the catalytic mechanisms of these enzymes is essential for understanding the molecular basis of mitochondrial diseases and aging...
  66. Mouse Modeling of Leigh Disease and Complex I Assembly
    Carl Pinkert; Fiscal Year: 2007
    ..As such, this project represents a first step toward developing therapeutic strategies and targeted interventions for debilitating mitochondrial disorders. [unreadable] [unreadable]..
  67. MITOCHONDRIAL CYTOCHROME C RELEASE VIA MEMBRANE PORES
    Elliott Crouser; Fiscal Year: 2004
    ..Through investigations of mitochondrial apoptotic pathways. this proposal will provide new insights into mitochondrial diseases and will establish the candidate's future in mitochondrial medical research...
  68. Functional Proteogenomics of Mitochondria
    Peter Oefner; Fiscal Year: 2005
    ..The concordance of protein data with those obtained by means of human mRNA expression arrays and the functional genomic findings from yeast will be assessed. ..
  69. Structure and Function of Iron-Sulfur Clusters
    Michael Weaver; Fiscal Year: 2009
    ..Defects in iron-sulfur cluster containing molecules are known to be associated with mitochondrial diseases, and the ability to better model these systems may lend new insight into diseases such as Parkinson's. ..
  70. CLINICAL STUDIES OF MITOCHONDRIAL DISEASE
    DONALD JOHNS; Fiscal Year: 2004
    DESCRIPTION (Adapted from The Applicant's Abstract): Mitochondrial diseases have protean clinical manifestations, including the nervous system and eye...