In vivo levels of mitochondrial hydrogen peroxide increase with age in mtDNA mutator mice |
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Authors: | Angela Logan Irina G. Shabalina Tracy A. Prime Sebastian Rogatti Anastasia V. Kalinovich Richard C. Hartley Ralph C. Budd Barbara Cannon Michael P. Murphy |
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Affiliation: | 1. MRC Mitochondrial Biology Unit, , Cambridge, CB2 0XY UK;2. Department of Molecular Biosciences, the Wenner‐Gren Institute, the Arrhenius Laboratories F3, Stockholm University, , Stockholm, SE‐106 91 Sweden;3. Centre for the Chemical Research of Ageing, WestCHEM School of Chemistry, University of Glasgow, , Glasgow, G12 8QQ UK;4. Vermont Center for Immunology & Infectious Diseases, The University of Vermont College of Medicine, , Burlington, VT, 05405‐0068 USA |
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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. |
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Keywords: | hydrogen peroxide MitoB mitochondria mitochondrial DNA mtDNA mutator mice |
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