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

Logan, A., Shabalina, I. G., Prime, T. A., Rogatti, S., Kalinovich, A. V., Hartley, R. C. , Budd, R. C., Cannon, B. and Murphy, M. P. (2014) In vivo levels of mitochondrial hydrogen peroxide increase with age in mtDNA mutator mice. Aging Cell, 13(4), pp. 765-768. (doi: 10.1111/acel.12212) (PMID:24621297) (PMCID:PMC4326952)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Hartley, Professor Richard
• Authors: Logan, A., Shabalina, I. G., Prime, T. A., Rogatti, S., Kalinovich, A. V., Hartley, R. C., Budd, R. C., Cannon, B., and Murphy, M. P.
• College/School: College of Science and Engineering > School of Chemistry
• Journal Name: Aging Cell
• Publisher: Wiley-Blackwell Publishing Ltd.
• ISSN: 1474-9718
• ISSN (Online): 1474-9726
• Copyright Holders: Copyright © 2014 The Authors
• First Published: First published in Aging Cell 13(4):765-768
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
55393	1	Developing chemical mass spectrometry probes to assess the production of reactive oxygen species in vivo	Richard Hartley	Biotechnology and Biological Sciences Research Council (BBSRC)	BB/I012826/1	CHEM - CHEMISTRY