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

Autor: Kruse SE; Department of Radiology, University of Washington, Seattle, WA, USA., Karunadharma PP; Department of Pathology, University of Washington, Seattle, WA, USA.; Scripps Research Institute, Jupiter, FL, USA., Basisty N; Department of Pathology, University of Washington, Seattle, WA, USA., Johnson R; Department of Genome Sciences, University of Washington, Seattle, WA, USA., Beyer RP; Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA., MacCoss MJ; Department of Genome Sciences, University of Washington, Seattle, WA, USA., Rabinovitch PS; Department of Pathology, University of Washington, Seattle, WA, USA., Marcinek DJ; Department of Radiology, University of Washington, Seattle, WA, USA.; Department of Pathology, University of Washington, Seattle, WA, USA.; Department of Bioengineering, University of Washington, Seattle, WA, USA.
Jazyk: angličtina
Zdroj: Aging cell [Aging Cell] 2016 Feb; Vol. 15 (1), pp. 89-99. Date of Electronic Publication: 2015 Oct 25.
DOI: 10.1111/acel.12412
Abstrakt: 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 H2 O2 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.
(© 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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