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  • Low abundance of the matrix arm of complex I in mitochondria predicts longevity in mice.

Low abundance of the matrix arm of complex I in mitochondria predicts longevity in mice.

Nature communications (2014-05-13)
Satomi Miwa, Howsun Jow, Karen Baty, Amy Johnson, Rafal Czapiewski, Gabriele Saretzki, Achim Treumann, Thomas von Zglinicki
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.

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