Gerald Shadel

Summary

Affiliation: Yale University
Country: USA

Publications

  1. pmc Expanding the mitochondrial interactome
    Timothy E Shutt
    Department of Pathology, Yale University School of Medicine, Cedar Street, New Haven, CT 06520 8023, USA
    Genome Biol 8:203. 2007
  2. ncbi request reprint Coupling the mitochondrial transcription machinery to human disease
    Gerald 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
  3. ncbi request reprint A dual-function mitochondrial transcription factor tunes out deafness
    Gerald 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
  4. ncbi request reprint Mitochondrial DNA, aconitase 'wraps' it up
    Gerald 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
  5. pmc Expression and maintenance of mitochondrial DNA: new insights into human disease pathology
    Gerald 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
  6. pmc Extension of chronological life span by reduced TOR signaling requires down-regulation of Sch9p and involves increased mitochondrial OXPHOS complex density
    Yong Pan
    Department of Pathology, Yale University School of Medicine, New Haven CT 06520, USA
    Aging (Albany NY) 1:131-45. 2009
  7. pmc Human mitochondrial ribosomal protein MRPL12 interacts directly with mitochondrial RNA polymerase to modulate mitochondrial gene expression
    Zhibo Wang
    Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06520 8023, USA
    J Biol Chem 282:12610-8. 2007
  8. pmc Cell cycle- and ribonucleotide reductase-driven changes in mtDNA copy number influence mtDNA Inheritance without compromising mitochondrial gene expression
    Maria 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
  9. pmc 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 deafness
    Justin 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
  10. ncbi request reprint Initiation and beyond: multiple functions of the human mitochondrial transcription machinery
    Nicholas 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

Collaborators

  • Michael Snyder
  • Hong Zhang
  • David A Clayton
  • Yajaira Suarez
  • - Zhang Hong
  • William Sessa
  • PAUL DOETSCH
  • Nicholas D Bonawitz
  • Justin Cotney
  • Timothy E Shutt
  • Maria A Lebedeva
  • Jana S Eaton
  • Yong Pan
  • Nicole A Doudican
  • Matthew S Rodeheffer
  • Vicki McCulloch
  • Bonnie L Seidel-Rogol
  • Zhibo Wang
  • Thomas W O'Rourke
  • Michal Caspi Tal
  • Michael Schleicher
  • Anthony C Bryan
  • Marc Chatenay-Lapointe
  • Anthony D D'Souza
  • Christopher M Wearn
  • Sean D Taylor
  • Paulo S R Coelho
  • Craig E Cameron
  • Maria F Lodeiro
  • Brian Yordy
  • Heung Kyu Lee
  • Akiko Iwasaki
  • Sharen E McKay
  • Miwa Sasai
  • Lisette M Acevedo
  • Carlos Fernandez-Hernando
  • Benjamin R Shepherd
  • Jun Yu
  • Alan C Sartorelli
  • Z Ping Lin
  • Susan M Kaech
  • Neal Parikh
  • Binwei Song
  • Wolfram Siede
  • Melinda D Mackereth
  • Anuj Kumar

Detail Information

Publications35

  1. pmc Expanding the mitochondrial interactome
    Timothy 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...
  2. ncbi request reprint Coupling the mitochondrial transcription machinery to human disease
    Gerald 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...
  3. ncbi request reprint A dual-function mitochondrial transcription factor tunes out deafness
    Gerald 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
  4. ncbi request reprint Mitochondrial DNA, aconitase 'wraps' it up
    Gerald 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...
  5. pmc Expression and maintenance of mitochondrial DNA: new insights into human disease pathology
    Gerald 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...
  6. pmc Extension of chronological life span by reduced TOR signaling requires down-regulation of Sch9p and involves increased mitochondrial OXPHOS complex density
    Yong Pan
    Department of Pathology, Yale University School of Medicine, New Haven CT 06520, USA
    Aging (Albany NY) 1:131-45. 2009
    ....
  7. pmc Human mitochondrial ribosomal protein MRPL12 interacts directly with mitochondrial RNA polymerase to modulate mitochondrial gene expression
    Zhibo 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...
  8. pmc Cell cycle- and ribonucleotide reductase-driven changes in mtDNA copy number influence mtDNA Inheritance without compromising mitochondrial gene expression
    Maria 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...
  9. pmc 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 deafness
    Justin 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
    ....
  10. ncbi request reprint Initiation and beyond: multiple functions of the human mitochondrial transcription machinery
    Nicholas 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
    ....
  11. pmc Defective mitochondrial gene expression results in reactive oxygen species-mediated inhibition of respiration and reduction of yeast life span
    Nicholas 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
    ....
  12. pmc Ataxia-telangiectasia mutated kinase regulates ribonucleotide reductase and mitochondrial homeostasis
    Jana 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...
  13. pmc A compendium of human mitochondrial gene expression machinery with links to disease
    Timothy E Shutt
    Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA
    Environ Mol Mutagen 51:360-79. 2010
    ....
  14. pmc Core human mitochondrial transcription apparatus is a regulated two-component system in vitro
    Timothy 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
    ....
  15. pmc The conserved Mec1/Rad53 nuclear checkpoint pathway regulates mitochondrial DNA copy number in Saccharomyces cerevisiae
    Sean 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...
  16. pmc Loss of p53 causes mitochondrial DNA depletion and altered mitochondrial reactive oxygen species homeostasis
    Maria 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...
  17. ncbi request reprint 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 mtTFB2
    Justin 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
    ....
  18. pmc Expression of the rDNA-encoded mitochondrial protein Tar1p is stringently controlled and responds differentially to mitochondrial respiratory demand and dysfunction
    Nicholas 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...
  19. pmc Reduced TOR signaling extends chronological life span via increased respiration and upregulation of mitochondrial gene expression
    Nicholas D Bonawitz
    Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, USA
    Cell Metab 5:265-77. 2007
    ....
  20. pmc Convergence of multiple signaling pathways is required to coordinately up-regulate mtDNA and mitochondrial biogenesis during T cell activation
    Anthony 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
    ....
  21. pmc A novel mitochondrial protein, Tar1p, is encoded on the antisense strand of the nuclear 25S rDNA
    Paulo S R Coelho
    Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520 8103, USA
    Genes Dev 16:2755-60. 2002
    ....
  22. ncbi request reprint Rethinking the mitochondrial theory of aging: the role of mitochondrial gene expression in lifespan determination
    Nicholas 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...
  23. pmc Absence of autophagy results in reactive oxygen species-dependent amplification of RLR signaling
    Michal 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
    ....
  24. pmc Prohibitin-1 maintains the angiogenic capacity of endothelial cells by regulating mitochondrial function and senescence
    Michael 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...
  25. pmc Mitochondrial dysfunction due to oxidative mitochondrial DNA damage is reduced through cooperative actions of diverse proteins
    Nicole 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...
  26. pmc Modulation of mitochondrial transcription in response to mtDNA depletion and repletion in HeLa cells
    Bonnie 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
    ....
  27. pmc A human mitochondrial transcription factor is related to RNA adenine methyltransferases and binds S-adenosylmethionine
    Vicki McCulloch
    Department of Biochemistry, Rollins Research Center, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    Mol Cell Biol 22:1116-25. 2002
    ....
  28. pmc Oxidative DNA damage causes mitochondrial genomic instability in Saccharomyces cerevisiae
    Nicole 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
    ....
  29. ncbi request reprint Human mitochondrial transcription factor B1 methylates ribosomal RNA at a conserved stem-loop
    Bonnie 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...
  30. pmc Multiple interactions involving the amino-terminal domain of yeast mtRNA polymerase determine the efficiency of mitochondrial protein synthesis
    Matthew 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
    ....
  31. pmc Relative abundance of the human mitochondrial transcription system and distinct roles for h-mtTFB1 and h-mtTFB2 in mitochondrial biogenesis and gene expression
    Justin 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
    ....
  32. ncbi request reprint Diagnostic assays for defects in mtDNA replication and transcription in yeast and humans
    Gerald S Shadel
    Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA
    Methods Cell Biol 80:465-79. 2007
  33. pmc Human mitochondrial transcription factor B1 interacts with the C-terminal activation region of h-mtTFA and stimulates transcription independently of its RNA methyltransferase activity
    Vicki 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...
  34. ncbi request reprint Differential involvement of the related DNA helicases Pif1p and Rrm3p in mtDNA point mutagenesis and stability
    Thomas 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...
  35. pmc Sls1p is a membrane-bound regulator of transcription-coupled processes involved in Saccharomyces cerevisiae mitochondrial gene expression
    Anthony C Bryan
    Department of Biochemistry, Rollins Research Center, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    Genetics 160:75-82. 2002
    ....

Research Grants21

  1. Mitochondrial Dysfunction and Oxidative Stress in Ataxia Telangiectasia
    Gerald S Shadel; Fiscal Year: 2010
    ....
  2. Nuclear Control of Mitochondrial Gene Expression
    Gerald 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. ..
  3. Mitochondrial Dysfunction and Oxidative Stress in Ataxia Telangiectasia
    Gerald S Shadel; Fiscal Year: 2010
    ....
  4. Epigenetic Regulation of Mitochondiral Complex II
    Gerald 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. ..
  5. Mitochondrial Dysfunction and Oxidative Stress in Ataxia Telangiectasia
    Gerald Shadel; Fiscal Year: 2007
    ....
  6. CONTROL OF MITOCHONDRIAL DNA REPLICATION IN HUMANS
    Gerald 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. ..
  7. Nuclear Control of Mitochondrial Gene Expression
    Gerald Shadel; Fiscal Year: 2003
    ..abstract_text> ..
  8. Nuclear Control of Mitochondrial Gene Expression
    Gerald Shadel; Fiscal Year: 2006
    ..abstract_text> ..