In vivo levels of mitochondrial hydrogen peroxide increase with age in mtDNA mutator mice.

TitleIn vivo levels of mitochondrial hydrogen peroxide increase with age in mtDNA mutator mice.
Publication TypeJournal Article
Year of Publication2014
AuthorsLogan, A, Shabalina, IG, Prime, TA, Rogatti, S, Kalinovich, AV, Hartley, RC, Budd, RC, Cannon, B, Murphy, MP
JournalAging Cell
Volume13
Issue4
Pagination765-8
Date Published2014 Aug
ISSN1474-9726
KeywordsAging, Animals, Cytokines, DNA, Mitochondrial, Hydrogen Peroxide, Lipopolysaccharides, Mice, Mitochondria, Mutation, Organophosphorus Compounds
Abstract

In mtDNA mutator mice, mtDNA mutations accumulate leading to a rapidly aging phenotype. However, there is little evidence of oxidative damage to tissues, and when analyzed ex vivo, no change in production of the reactive oxygen species (ROS) superoxide and hydrogen peroxide by mitochondria has been reported, undermining the mitochondrial oxidative damage theory of aging. Paradoxically, interventions that decrease mitochondrial ROS levels in vivo delay onset of aging. To reconcile these findings, we used the mitochondria-targeted mass spectrometry probe MitoB to measure hydrogen peroxide within mitochondria of living mice. Mitochondrial hydrogen peroxide was the same in young mutator and control mice, but as the mutator mice aged, hydrogen peroxide increased. This suggests that the prolonged presence of mtDNA mutations in vivo increases hydrogen peroxide that contributes to an accelerated aging phenotype, perhaps through the activation of pro-apoptotic and pro-inflammatory redox signaling pathways.

DOI10.1111/acel.12212
Alternate JournalAging Cell
Citation Key10.1111/acel.12212
PubMed ID24621297
PubMed Central IDPMC4326952
Grant ListMC_U105663142 / / Medical Research Council / United Kingdom