期刊
NATURE COMMUNICATIONS
卷 5, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms4837
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资金
- Biotechnology and Biological Sciences Research Council (BBSRC) [BB/C008200/1, BB/I020748/1]
- BBSRC/CBSL
- Biotechnology and Biological Sciences Research Council [BB/I020748/1, BB/F010966/1, BB/C008200/1] Funding Source: researchfish
- BBSRC [BB/I020748/1, BB/F010966/1] Funding Source: UKRI
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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