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In vivo levels of mitochondrial hydrogen peroxide increase with age in mtDNA mutator mice
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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BlackWell Publishing Ltd
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326952/ https://www.ncbi.nlm.nih.gov/pubmed/24621297 http://dx.doi.org/10.1111/acel.12212 |
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author | Logan, Angela Shabalina, Irina G Prime, Tracy A Rogatti, Sebastian Kalinovich, Anastasia V Hartley, Richard C Budd, Ralph C Cannon, Barbara Murphy, Michael P |
author_facet | Logan, Angela Shabalina, Irina G Prime, Tracy A Rogatti, Sebastian Kalinovich, Anastasia V Hartley, Richard C Budd, Ralph C Cannon, Barbara Murphy, Michael P |
author_sort | Logan, Angela |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4326952 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BlackWell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-43269522015-02-19 In vivo levels of mitochondrial hydrogen peroxide increase with age in mtDNA mutator mice Logan, Angela Shabalina, Irina G Prime, Tracy A Rogatti, Sebastian Kalinovich, Anastasia V Hartley, Richard C Budd, Ralph C Cannon, Barbara Murphy, Michael P Aging Cell Short Takes 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. BlackWell Publishing Ltd 2014-08 2014-03-13 /pmc/articles/PMC4326952/ /pubmed/24621297 http://dx.doi.org/10.1111/acel.12212 Text en © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. http://creativecommons.org/licenses/by/3.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Short Takes Logan, Angela Shabalina, Irina G Prime, Tracy A Rogatti, Sebastian Kalinovich, Anastasia V Hartley, Richard C Budd, Ralph C Cannon, Barbara Murphy, Michael P In vivo levels of mitochondrial hydrogen peroxide increase with age in mtDNA mutator mice |
title | In vivo levels of mitochondrial hydrogen peroxide increase with age in mtDNA mutator mice |
title_full | In vivo levels of mitochondrial hydrogen peroxide increase with age in mtDNA mutator mice |
title_fullStr | In vivo levels of mitochondrial hydrogen peroxide increase with age in mtDNA mutator mice |
title_full_unstemmed | In vivo levels of mitochondrial hydrogen peroxide increase with age in mtDNA mutator mice |
title_short | In vivo levels of mitochondrial hydrogen peroxide increase with age in mtDNA mutator mice |
title_sort | in vivo levels of mitochondrial hydrogen peroxide increase with age in mtdna mutator mice |
topic | Short Takes |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326952/ https://www.ncbi.nlm.nih.gov/pubmed/24621297 http://dx.doi.org/10.1111/acel.12212 |
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