Low abundance of the matrix arm of complex I in mitochondria predicts longevity in mice
Satomi Miwa,
Howsun Jow,
Karen Baty,
Amy Johnson,
Rafal Czapiewski,
Gabriele Saretzki,
Achim Treumann and
Thomas von Zglinicki ()
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Satomi Miwa: Institute for Ageing and Health, Newcastle University
Howsun Jow: Centre for Integrated Systems Biology of Ageing and Nutrition, Newcastle University
Karen Baty: Newcastle University Protein and Proteome Analysis, Devonshire Building, Devonshire Terrace
Amy Johnson: Institute for Ageing and Health, Newcastle University
Rafal Czapiewski: Institute for Ageing and Health, Newcastle University
Gabriele Saretzki: Institute for Ageing and Health, Newcastle University
Achim Treumann: Newcastle University Protein and Proteome Analysis, Devonshire Building, Devonshire Terrace
Thomas von Zglinicki: Institute for Ageing and Health, Newcastle University
Nature Communications, 2014, vol. 5, issue 1, 1-12
Abstract:
Abstract Mitochondrial function is an important determinant of the ageing process; however, the mitochondrial properties that enable longevity are not well understood. Here we show that optimal assembly of mitochondrial complex I predicts longevity in mice. Using an unbiased high-coverage high-confidence approach, we demonstrate that electron transport chain proteins, especially the matrix arm subunits of complex I, are decreased in young long-living mice, which is associated with improved complex I assembly, higher complex I-linked state 3 oxygen consumption rates and decreased superoxide production, whereas the opposite is seen in old mice. Disruption of complex I assembly reduces oxidative metabolism with concomitant increase in mitochondrial superoxide production. This is rescued by knockdown of the mitochondrial chaperone, prohibitin. Disrupted complex I assembly causes premature senescence in primary cells. We propose that lower abundance of free catalytic complex I components supports complex I assembly, efficacy of substrate utilization and minimal ROS production, enabling enhanced longevity.
Date: 2014
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4837
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DOI: 10.1038/ncomms4837
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