Age modifies respiratory complex I and protein homeostasis in a muscle type‐specific manner

Changes in mitochondrial function with age vary between different muscle types, and mechanisms underlying this variation remain poorly defined. We examined whether the rate of mitochondrial protein turnover contributes to this variation. Using heavy label proteomics, we measured mitochondrial protei...

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Main Authors:	Kruse, Shane E., Karunadharma, Pabalu P., Basisty, Nathan, Johnson, Richard, Beyer, Richard P., MacCoss, Michael J., Rabinovitch, Peter S., Marcinek, David J.
Format:	Online
Language:	English
Published:	John Wiley and Sons Inc. 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4717270/

id	pubmed-4717270
recordtype	oai_dc
spelling	pubmed-47172702016-01-31 Age modifies respiratory complex I and protein homeostasis in a muscle type‐specific manner Kruse, Shane E. Karunadharma, Pabalu P. Basisty, Nathan Johnson, Richard Beyer, Richard P. MacCoss, Michael J. Rabinovitch, Peter S. Marcinek, David J. Original Articles Changes in mitochondrial function with age vary between different muscle types, and mechanisms underlying this variation remain poorly defined. We examined whether the rate of mitochondrial protein turnover contributes to this variation. Using heavy label proteomics, we measured mitochondrial protein turnover and abundance in slow‐twitch soleus (SOL) and fast‐twitch extensor digitorum longus (EDL) from young and aged mice. We found that mitochondrial proteins were longer lived in EDL than SOL at both ages. Proteomic analyses revealed that age‐induced changes in protein abundance differed between EDL and SOL with the largest change being increased mitochondrial respiratory protein content in EDL. To determine how altered mitochondrial proteomics affect function, we measured respiratory capacity in permeabilized SOL and EDL. The increased mitochondrial protein content in aged EDL resulted in reduced complex I respiratory efficiency in addition to increased complex I‐derived H2O2 production. In contrast, SOL maintained mitochondrial quality, but demonstrated reduced respiratory capacity with age. Thus, the decline in mitochondrial quality with age in EDL was associated with slower protein turnover throughout life that may contribute to the greater decline in mitochondrial dysfunction in this muscle. Furthermore, mitochondrial‐targeted catalase protected respiratory function with age suggesting a causal role of oxidative stress. Our data clearly indicate divergent effects of age between different skeletal muscles on mitochondrial protein homeostasis and function with the greatest differences related to complex I. These results show the importance of tissue‐specific changes in the interaction between dysregulation of respiratory protein expression, oxidative stress, and mitochondrial function with age. John Wiley and Sons Inc. 2015-10-25 2016-02 /pmc/articles/PMC4717270/ /pubmed/26498839 http://dx.doi.org/10.1111/acel.12412 Text en © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Kruse, Shane E. Karunadharma, Pabalu P. Basisty, Nathan Johnson, Richard Beyer, Richard P. MacCoss, Michael J. Rabinovitch, Peter S. Marcinek, David J.
spellingShingle	Kruse, Shane E. Karunadharma, Pabalu P. Basisty, Nathan Johnson, Richard Beyer, Richard P. MacCoss, Michael J. Rabinovitch, Peter S. Marcinek, David J. Age modifies respiratory complex I and protein homeostasis in a muscle type‐specific manner
author_facet	Kruse, Shane E. Karunadharma, Pabalu P. Basisty, Nathan Johnson, Richard Beyer, Richard P. MacCoss, Michael J. Rabinovitch, Peter S. Marcinek, David J.
author_sort	Kruse, Shane E.
title	Age modifies respiratory complex I and protein homeostasis in a muscle type‐specific manner
title_short	Age modifies respiratory complex I and protein homeostasis in a muscle type‐specific manner
title_full	Age modifies respiratory complex I and protein homeostasis in a muscle type‐specific manner
title_fullStr	Age modifies respiratory complex I and protein homeostasis in a muscle type‐specific manner
title_full_unstemmed	Age modifies respiratory complex I and protein homeostasis in a muscle type‐specific manner
title_sort	age modifies respiratory complex i and protein homeostasis in a muscle type‐specific manner
description	Changes in mitochondrial function with age vary between different muscle types, and mechanisms underlying this variation remain poorly defined. We examined whether the rate of mitochondrial protein turnover contributes to this variation. Using heavy label proteomics, we measured mitochondrial protein turnover and abundance in slow‐twitch soleus (SOL) and fast‐twitch extensor digitorum longus (EDL) from young and aged mice. We found that mitochondrial proteins were longer lived in EDL than SOL at both ages. Proteomic analyses revealed that age‐induced changes in protein abundance differed between EDL and SOL with the largest change being increased mitochondrial respiratory protein content in EDL. To determine how altered mitochondrial proteomics affect function, we measured respiratory capacity in permeabilized SOL and EDL. The increased mitochondrial protein content in aged EDL resulted in reduced complex I respiratory efficiency in addition to increased complex I‐derived H2O2 production. In contrast, SOL maintained mitochondrial quality, but demonstrated reduced respiratory capacity with age. Thus, the decline in mitochondrial quality with age in EDL was associated with slower protein turnover throughout life that may contribute to the greater decline in mitochondrial dysfunction in this muscle. Furthermore, mitochondrial‐targeted catalase protected respiratory function with age suggesting a causal role of oxidative stress. Our data clearly indicate divergent effects of age between different skeletal muscles on mitochondrial protein homeostasis and function with the greatest differences related to complex I. These results show the importance of tissue‐specific changes in the interaction between dysregulation of respiratory protein expression, oxidative stress, and mitochondrial function with age.
publisher	John Wiley and Sons Inc.
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4717270/
_version_	1613525286601621504

Age modifies respiratory complex I and protein homeostasis in a muscle type‐specific manner

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