Research Topics
| Gerald ShadelSummaryAffiliation: Yale University Country: USA Publications
Research Grants
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Detail Information
Publications
Expanding the mitochondrial interactomeTimothy E Shutt
Department of Pathology, Yale University School of Medicine, Cedar Street, New Haven, CT 06520 8023, USA
Genome Biol 8:203. 2007..The integration of information on different aspects of the composition and function of mitochondria is defining a more comprehensive mitochondrial interactome and elucidating its role in a multitude of cellular processes and human disease...
Coupling the mitochondrial transcription machinery to human diseaseGerald S Shadel
Department of Pathology, Yale University School of Medicine, 300 Cedar Street, PO Box 208023, New Haven, CT 06520 8023, USA
Trends Genet 20:513-9. 2004..Defects in an analogous coupling mechanism in humans might underlie the cytochrome oxidase deficiency that causes a form of Leigh Syndrome...- A dual-function mitochondrial transcription factor tunes out deafnessGerald S Shadel
Department of Pathology, Yale University School of Medicine, 310 Cedar Street, New Haven, CT 06520-8023, USA
Mol Genet Metab 82:1-3. 2004 - Mitochondrial DNA, aconitase 'wraps' it upGerald S Shadel
Department of Pathology, Yale University School of Medicine, P O Box 208023, New Haven, CT 06520 8023, USA
Trends Biochem Sci 30:294-6. 2005..In this novel context, aconitase functions to stabilize mtDNA, perhaps by reversibly remodeling nucleoids to directly influence mitochondrial gene expression in response to changing cellular metabolism... - Expression and maintenance of mitochondrial DNA: new insights into human disease pathologyGerald S Shadel
Departments of Pathology and Genetics, Yale University School of Medicine, 310 Cedar St, P O Box 208023, New Haven, CT 06520 8023
Am J Pathol 172:1445-56. 2008..These advancements embody the current mitochondrial research landscape, which can be described as exploding with discoveries of previously unanticipated roles for mitochondria in human disease and aging... - Extension of chronological life span by reduced TOR signaling requires down-regulation of Sch9p and involves increased mitochondrial OXPHOS complex densityYong Pan
Department of Pathology, Yale University School of Medicine, New Haven CT 06520, USA
Aging (Albany NY) 1:131-45. 2009.... - Human mitochondrial ribosomal protein MRPL12 interacts directly with mitochondrial RNA polymerase to modulate mitochondrial gene expressionZhibo Wang
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06520 8023, USA
J Biol Chem 282:12610-8. 2007..We speculate that the MRPL12 interaction with POLRMT is likely part of a novel regulatory mechanism that coordinates mitochondrial transcription with translation and/or ribosome biogenesis during human mitochondrial gene expression... - Cell cycle- and ribonucleotide reductase-driven changes in mtDNA copy number influence mtDNA Inheritance without compromising mitochondrial gene expressionMaria A Lebedeva
Department of Pathology, and Graduate Program in Genetics, Yale University School of Medicine, New Haven, Connecticut 06520, USA
Cell Cycle 6:2048-57. 2007..These results indicate that one role for multiple mtDNA copies is to ensure optimal inheritance of mtDNA during cell division... - Elucidation of separate, but collaborative functions of the rRNA methyltransferase-related human mitochondrial transcription factors B1 and B2 in mitochondrial biogenesis reveals new insight into maternally inherited deafnessJustin Cotney
Department of Pathology, Yale University School of Medicine, 310 Cedar Street, PO Box 208023, New Haven, CT 06520 8023, USA
Hum Mol Genet 18:2670-82. 2009.... - Initiation and beyond: multiple functions of the human mitochondrial transcription machineryNicholas D Bonawitz
Department of Pathology, Yale University School of Medicine, 310 Cedar Street, P.O. Box 208023, New Haven, Connecticut 06520, USA
Mol Cell 24:813-25. 2006.... - Defective mitochondrial gene expression results in reactive oxygen species-mediated inhibition of respiration and reduction of yeast life spanNicholas D Bonawitz
Department of Pathology, Yale University School of Medicine, 310 Cedar St, P O Box 208023, New Haven, CT 06520 8023, USA
Mol Cell Biol 26:4818-29. 2006.... - Ataxia-telangiectasia mutated kinase regulates ribonucleotide reductase and mitochondrial homeostasisJana S Eaton
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06520 8023, USA
J Clin Invest 117:2723-34. 2007..Based on these results, we propose that disruption of RR and mitochondrial homeostasis contributes to the complex pathology of A-T and that RR genes are candidate disease loci in mtDNA-depletion syndromes... - A compendium of human mitochondrial gene expression machinery with links to diseaseTimothy E Shutt
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA
Environ Mol Mutagen 51:360-79. 2010.... - Core human mitochondrial transcription apparatus is a regulated two-component system in vitroTimothy E Shutt
Department of Pathology, Yale University School of Medicine, 310 Cedar Street, PO Box 208023, New Haven, CT 06520 8023, USA
Proc Natl Acad Sci U S A 107:12133-8. 2010.... - The conserved Mec1/Rad53 nuclear checkpoint pathway regulates mitochondrial DNA copy number in Saccharomyces cerevisiaeSean D Taylor
Department of Pathology, Yale University School of Medicine, New Haven, CT 06520 8023, USA
Mol Biol Cell 16:3010-8. 2005..This comprises the first linkage of a conserved signaling pathway to the regulation of mitochondrial genome copy number and suggests that homologous pathways in humans may likewise regulate mtDNA content under physiological conditions... - Loss of p53 causes mitochondrial DNA depletion and altered mitochondrial reactive oxygen species homeostasisMaria A Lebedeva
Department of Pathology, Yale University School of Medicine, New Haven, CT 06520 8023, USA
Biochim Biophys Acta 1787:328-34. 2009..Altogether, these results elucidate additional mitochondria-related functions for p53 and implicate mtDNA depletion and ROS alterations as potentially relevant to cellular transformation, cancer cell phenotypes, and the Warburg Effect... - Evidence for an early gene duplication event in the evolution of the mitochondrial transcription factor B family and maintenance of rRNA methyltransferase activity in human mtTFB1 and mtTFB2Justin Cotney
Department of Pathology, Yale University School of Medicine, 310 Cedar Street, PO Box 208023, New Haven, CT 06520 8023, USA
J Mol Evol 63:707-17. 2006.... - Expression of the rDNA-encoded mitochondrial protein Tar1p is stringently controlled and responds differentially to mitochondrial respiratory demand and dysfunctionNicholas D Bonawitz
Department of Pathology and Genetics, Yale University School of Medicine, 310 Cedar Street, P O Box 208023, New Haven, CT 06520 8023, USA
Curr Genet 54:83-94. 2008..Furthermore, we speculate that Tar1p is down-regulated when respiration is defective to prevent deleterious ROS-dependent consequences of mitochondrial dysfunction... - Reduced TOR signaling extends chronological life span via increased respiration and upregulation of mitochondrial gene expressionNicholas D Bonawitz
Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, USA
Cell Metab 5:265-77. 2007.... - Convergence of multiple signaling pathways is required to coordinately up-regulate mtDNA and mitochondrial biogenesis during T cell activationAnthony D D'Souza
Department of Pathology, Yale University School of Medicine, 310 Cedar Street, P O Box 208023, New Haven, CT 06520 8023, USA
Mitochondrion 7:374-85. 2007.... - A novel mitochondrial protein, Tar1p, is encoded on the antisense strand of the nuclear 25S rDNAPaulo S R Coelho
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520 8103, USA
Genes Dev 16:2755-60. 2002.... - Rethinking the mitochondrial theory of aging: the role of mitochondrial gene expression in lifespan determinationNicholas D Bonawitz
Department of Pathology, School of Medicine, Yale University, New Haven, Connecticut 06520, USA
Cell Cycle 6:1574-8. 2007..We speculate that this form of mitochondrial dysfunction may operate independently or in concert with mtDNA mutations to promote age-related pathology and limit lifespan... - Absence of autophagy results in reactive oxygen species-dependent amplification of RLR signalingMichal Caspi Tal
Department of Immunobiology, Pathology, and Genetics, Yale University School of Medicine, New Haven, CT 06520, USA
Proc Natl Acad Sci U S A 106:2770-5. 2009.... - Prohibitin-1 maintains the angiogenic capacity of endothelial cells by regulating mitochondrial function and senescenceMichael Schleicher
Department of Pharmacology, and Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06536, USA
J Cell Biol 180:101-12. 2008..Collectively, our results provide evidence that PHB1 is important for mitochondrial function and prevents reactive oxygen species-induced senescence and thereby maintains the angiogenic capacity of endothelial cells... - Mitochondrial dysfunction due to oxidative mitochondrial DNA damage is reduced through cooperative actions of diverse proteinsNicole A Doudican
Department of Biochemistry, Emory University School of Medicine, Rollins Research Center, Emory University, Atlanta, Georgia 30322, USA
Mol Cell Biol 22:4086-93. 2002..Such systems are likely relevant to those operating in human cells where mtDNA recombination is less prevalent, validating yeast as a model system in which to study these important issues... - Modulation of mitochondrial transcription in response to mtDNA depletion and repletion in HeLa cellsBonnie L Seidel-Rogol
Department of Biochemistry, Rollins Research Center, Emory University School of Medicine, Atlanta, GA 30322, USA
Nucleic Acids Res 30:1929-34. 2002.... - A human mitochondrial transcription factor is related to RNA adenine methyltransferases and binds S-adenosylmethionineVicki McCulloch
Department of Biochemistry, Rollins Research Center, Emory University School of Medicine, Atlanta, Georgia 30322, USA
Mol Cell Biol 22:1116-25. 2002.... - Oxidative DNA damage causes mitochondrial genomic instability in Saccharomyces cerevisiaeNicole A Doudican
Department of Biochemistry, Graduate Program in Genetic and Molecular Biology, Emory University School of Medicine, 4013 Rollins Research Center, Atlanta, GA 30322, USA
Mol Cell Biol 25:5196-204. 2005.... - Human mitochondrial transcription factor B1 methylates ribosomal RNA at a conserved stem-loopBonnie L Seidel-Rogol
Department of Biochemistry, Rollins Research Center, Emory University School of Medicine, Atlanta, Georgia 30322 3050, USA
Nat Genet 33:23-4. 2003..Thus, h-mtTFB1 appears to be dual-function protein, acting both as a transcription factor and an rRNA-modification enzyme... - Multiple interactions involving the amino-terminal domain of yeast mtRNA polymerase determine the efficiency of mitochondrial protein synthesisMatthew S Rodeheffer
Department of Biochemistry and the Graduate Program in Biochemistry, Cell and Developmental Biology, Rollins Research Center, Emory University School of Medicine, Atlanta, Georgia 30322 3050, USA
J Biol Chem 278:18695-701. 2003.... - Relative abundance of the human mitochondrial transcription system and distinct roles for h-mtTFB1 and h-mtTFB2 in mitochondrial biogenesis and gene expressionJustin Cotney
Graduate Program in Genetics and Molecular Biology, Emory University School of Medicine, 440 Clifton Road N E, Atlanta, Georgia 30322, USA
Nucleic Acids Res 35:4042-54. 2007.... - Diagnostic assays for defects in mtDNA replication and transcription in yeast and humansGerald S Shadel
Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA
Methods Cell Biol 80:465-79. 2007 - Human mitochondrial transcription factor B1 interacts with the C-terminal activation region of h-mtTFA and stimulates transcription independently of its RNA methyltransferase activityVicki McCulloch
Department of Biochemistry, Rollins Research Center, Emory University School of Medicine, Atlanta, Georgia 30322 3050, USA
Mol Cell Biol 23:5816-24. 2003..Altogether, these data provide important new insight into the mechanism of transcription initiation in human mitochondria and indicate that the dual functions of h-mtTFB1 can be separated... - Differential involvement of the related DNA helicases Pif1p and Rrm3p in mtDNA point mutagenesis and stabilityThomas W O'Rourke
Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322 3050, USA
Gene 354:86-92. 2005..Altogether, our results define a novel role for Rrm3p in mitochondrial function and indicate that Pif1p and Rrm3p influence a common process (or processes) involved in mtDNA replication, repair, or stability... - Sls1p is a membrane-bound regulator of transcription-coupled processes involved in Saccharomyces cerevisiae mitochondrial gene expressionAnthony C Bryan
Department of Biochemistry, Rollins Research Center, Emory University School of Medicine, Atlanta, Georgia 30322, USA
Genetics 160:75-82. 2002....
Research Grants
- Mitochondrial Dysfunction and Oxidative Stress in Ataxia TelangiectasiaGerald S Shadel; Fiscal Year: 2010....
- Nuclear Control of Mitochondrial Gene ExpressionGerald S Shadel; Fiscal Year: 2010..This proposal is focused on understanding how mtDNA is regulated in human cells and will generate mouse models for how mitochondrial deficiencies causes heart disease. ..
- Mitochondrial Dysfunction and Oxidative Stress in Ataxia TelangiectasiaGerald S Shadel; Fiscal Year: 2010....
- Epigenetic Regulation of Mitochondiral Complex IIGerald S Shadel; Fiscal Year: 2010..Understanding the molecular basis of imprinting in PGL may provide general insights on how differential expression of a single defective gene can lead to disease or normalcy. ..
- Mitochondrial Dysfunction and Oxidative Stress in Ataxia TelangiectasiaGerald Shadel; Fiscal Year: 2007....
- CONTROL OF MITOCHONDRIAL DNA REPLICATION IN HUMANSGerald Shadel; Fiscal Year: 2000..The applicant's ability to pinpoint, and perhaps counteract, the pathogenic effects of defective mtDNA will come from elucidating pathways that connect the nuclear and mitochondrial genetic compartments in this manner. ..
- Nuclear Control of Mitochondrial Gene ExpressionGerald Shadel; Fiscal Year: 2006..abstract_text> ..