Kruse 2015 Aging Cell

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Kruse SE, Karunadharma PP, Basisty N, Johnson R, Beyer RP, MacCoss MJ, Rabinovitch PS, Marcinek DJ (2015) Age modifies respiratory complex I and protein homeostasis in a muscle type-specific manner. Aging Cell 15:89-99.

» PMID: 26498839

Kruse SE, Karunadharma PP, Basisty N, Johnson R, Beyer RP, MacCoss MJ, Rabinovitch PS, Marcinek DJ (2015) Aging Cell

Abstract: 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.

Keywords: Aging, Mitochondria, Mitochondrial dysfunction, Protein turnover, Proteome, Skeletal muscle, Amplex Red

O2k-Network Lab: US WA Seattle Kushmerick MJ, US WA Seattle Marcinek DJ


Labels: MiParea: Respiration, mt-Biogenesis;mt-density  Pathology: Aging;senescence  Stress:Oxidative stress;RONS  Organism: Mouse  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue  Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase 

Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, CIV, NS, ROX  HRR: Oxygraph-2k