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

AuthorCount:9;
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.

Shabalina, Irina G.Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut(Swepub:su)chaba (author)
Prime, Tracy A. (author)
Rogatti, Sebastian (author)
Kalinovich, Anastasia V.Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut(Swepub:su)akali (author)
Hartley, Richard C. (author)
Budd, Ralph C. (author)
Cannon, BarbaraStockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut(Swepub:su)canno (author)
Murphy, Michael P. (author)
Stockholms universitetInstitutionen för molekylär biovetenskap, Wenner-Grens institut (creator_code:org_t)

By the author/editor: Logan, Angela; Shabalina, Irina ...; Prime, Tracy A.; Rogatti, Sebasti ...; Kalinovich, Anas ...; Hartley, Richard ...; show more...; Budd, Ralph C.; Cannon, Barbara; Murphy, Michael ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Cell and Molecul ...

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Biochemistry and ...

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