Mitochondrial DNA mutations induce mitochondrial dysfunction, apoptosis and sarcopenia in skeletal muscle of mitochondrial DNA mutator mice.

PloS One
Asimina HionaChristiaan Leeuwenburgh

Abstract

Aging results in a progressive loss of skeletal muscle, a condition known as sarcopenia. Mitochondrial DNA (mtDNA) mutations accumulate with aging in skeletal muscle and correlate with muscle loss, although no causal relationship has been established. We investigated the relationship between mtDNA mutations and sarcopenia at the gene expression and biochemical levels using a mouse model that expresses a proofreading-deficient version (D257A) of the mitochondrial DNA Polymerase gamma, resulting in increased spontaneous mtDNA mutation rates. Gene expression profiling of D257A mice followed by Parametric Analysis of Gene Set Enrichment (PAGE) indicates that the D257A mutation is associated with a profound downregulation of gene sets associated with mitochondrial function. At the biochemical level, sarcopenia in D257A mice is associated with a marked reduction (35-50%) in the content of electron transport chain (ETC) complexes I, III and IV, all of which are partly encoded by mtDNA. D257A mice display impaired mitochondrial bioenergetics associated with compromised state-3 respiration, lower ATP content and a resulting decrease in mitochondrial membrane potential (Deltapsim). Surprisingly, mitochondrial dysfunction was not accompan...Continue Reading

References

Jan 31, 1992·Biochemical and Biophysical Research Communications·H YamamotoT Ozawa
Jun 1, 1990·Anatomia, histologia, embryologia·D L TroyerH W Leipold
Jan 1, 1990·Free Radical Biology & Medicine·B Bandy, A J Davison
Dec 11, 1990·Nucleic Acids Research·G A Cortopassi, N Arnheim
Apr 1, 1972·Journal of the American Geriatrics Society·D Harman
Aug 1, 1972·The American Journal of Clinical Nutrition·D Harman
Jan 1, 1982·Journal of the American College of Nutrition·D Harman
Jun 1, 1995·Journal of Applied Physiology·D N ProctorP W Lemon
Jan 1, 1993·Virchows Archiv. A, Pathological Anatomy and Histopathology·J Müller-HöckerB Kadenbach
Jun 1, 1994·Aging : Clinical and Experimental Research·S S ChungJ M Aiken
Mar 25, 1994·Nucleic Acids Research·S MelovT E Johnson
Feb 1, 1996·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·J G de la AsuncionJ Viña
Sep 1, 1996·Archives of Biochemistry and Biophysics·V G DesaiR J Feuers
Apr 1, 1997·Proceedings of the National Academy of Sciences of the United States of America·T M HagenB N Ames
Jan 6, 1999·Biophysical Journal·R C Scaduto, L W Grotyohann
Apr 24, 1999·Biochimie·V A Bohr, G L Dianov
Feb 5, 2000·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·G Barja, A Herrero
Oct 21, 2000·European Journal of Clinical Nutrition·R Roubenoff
Feb 7, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·J WanagatJ M Aiken
Mar 17, 2001·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·S B LalM E Harper
Mar 29, 2001·Proceedings of the National Academy of Sciences of the United States of America·Y WangG Attardi
Oct 12, 2001·American Journal of Physiology. Endocrinology and Metabolism·J KernerC L Hoppel
Jan 17, 2002·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Amie Dirks, Christiaan Leeuwenburgh
Feb 21, 2002·Proceedings of the National Academy of Sciences of the United States of America·Tory M HagenBruce N Ames
May 3, 2002·European Journal of Biochemistry·Debbie McKenzieUNKNOWN Jonathan Wanagat
May 17, 2002·Journal of Applied Physiology·Entela A BuaJudd M Aiken
Aug 13, 2002·Journal of Bioenergetics and Biomembranes·Gustavo Barja

❮ Previous
Next ❯

Citations

Feb 13, 2014·Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology·Carolyn P Ojano-DirainColleen G Le Prell
May 28, 2014·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Radek SzklarczykHeinz D Osiewacz
May 18, 2011·Journal of Aging Research·Claus DeslerLene Juel Rasmussen
Jul 19, 2014·Trends in Endocrinology and Metabolism : TEM·Emma P K Yu, Martin R Bennett
Feb 8, 2011·Nutrition Reviews·Manuel SchiffPierre Rustin
May 24, 2014·Alcohol and Alcoholism : International Journal of the Medical Council on Alcoholism·D LaurentJ G Edwards
Jan 30, 2014·Longevity & Healthspan·James N CobleyGraeme L Close
Mar 4, 2011·Proceedings of the National Academy of Sciences of the United States of America·Adeel SafdarMark A Tarnopolsky
May 5, 2011·Antioxidants & Redox Signaling·John M Lawler, Allyson Hindle
Feb 24, 2012·Human Molecular Genetics·Lloye M DillonCarlos T Moraes
Jun 22, 2012·Journal of Aging Research·Claus DeslerLene Juel Rasmussen
Feb 5, 2013·American Journal of Physiology. Heart and Circulatory Physiology·S HicksJ G Edwards
Mar 31, 2012·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Martin P HoranJ William O Ballard
Jan 11, 2013·Journal of Human Genetics·Martin Patrick HoranJ William O Ballard
May 11, 2011·Antioxidants & Redox Signaling·Lucia BiasuttoMario Zoratti
Dec 17, 2011·Journal of Signal Transduction·Saverio MarchiPaolo Pinton
Aug 14, 2012·Journal of Aging Research·Courtney M PetersonEric Ravussin
Nov 29, 2012·Rejuvenation Research·Catalina SantiagoAlejandro Lucia
Sep 18, 2012·Free Radical Biology & Medicine·Kristine Ansenberger-FricanoMarcelo G Bonini
Dec 6, 2011·Mechanisms of Ageing and Development·Peter SykoraVilhelm A Bohr
Oct 27, 2011·Experimental Gerontology·María del R CastroSylvette Ayala-Torres
Dec 15, 2015·The International Journal of Biochemistry & Cell Biology·Bipasha Bose, P Sudheer Shenoy
Nov 6, 2015·Ageing Research Reviews·Jessie Van HouckeLieve Moons
Mar 23, 2011·Journal of Aging Research·Reinald Pamplona
Oct 10, 2014·Scientific Reports·Jaime M RossLars Olson
Aug 22, 2015·Neurobiology of Aging·Joanne Clark-MatottDavid K Simon
Sep 20, 2011·Journal of Cellular Physiology·Sébastien MichelPatricia Renard
Jan 27, 2012·IUBMB Life·Lloye M DillonCarlos T Moraes
Sep 25, 2012·Environmental and Molecular Mutagenesis·Miriam R Menezes, Joann B Sweasy
Mar 22, 2016·Biochimica Et Biophysica Acta·Alberto Sanz

❮ Previous
Next ❯

Methods Mentioned

BETA
electrophoresis
ELISA
PCR
protease assay
laser capture microdissection
chips

Software Mentioned

Graph
Parametric Analysis of Gene Set Enrichment ( PAGE )
Image J
- Pad Prism
EZChrome Elite

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis