Post-translational decrease in respiratory chain proteins in the Polg mutator mouse brain.
Mitochondrial DNA damage is thought to be a causal contributor to aging as mice with inactivating mutations in polymerase gamma (Polg) develop a progeroid phenotype. To further understand the molecular mechanisms underlying this phenotype, we used iTRAQ and RNA-Seq to determine differences in protein and mRNA abundance respectively in the brains of one year old Polg mutator mice compared to control animals. We found that mitochondrial respiratory chain proteins are specifically decreased in abundance in the brains of the mutator mice, including several nuclear encoded mitochondrial components. However, we found no evidence that the changes we observed in protein levels were the result of decreases in mRNA expression. These results show that there are post-translational effects associated with mutations in Polg.
Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America; Brown University/National Institutes of Health Graduate Partnership Program, Department of Neuroscience, Brown University, Providence, Rhode Island, United States of America.
David N
DN
Hauser
Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America; Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Allissa A
AA
Dillman
Computational Biology Unit, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America.
Jinhui
J
Ding
Protein/Peptide Sequencing Facility, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, United States of America.
Yan
Y
Li
Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, United States of America.
Mark R
MR
Cookson
D000818:Animals; D001921:Brain / Q000378:metabolism*; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000235:genetics; D004259:DNA-Directed DNA Polymerase / Q000235:genetics* / Q000378:metabolism; D004579:Electron Transport / Q000235:genetics*; D051379:Mice; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D010641:Phenotype; D014176:Protein Biosynthesis / Q000502:physiology*
D004272:DNA, Mitochondrial; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C498803:Polg protein, mouse