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.
复制标题
线粒体中复合物I的基质臂的低丰度预测小鼠的寿命。
DOI：
10.1038/ncomms4837
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发表时间：
2014-05-12
影响因子：
16.6
通讯作者：
von Zglinicki, Thomas
中科院分区：
文献类型：
--
作者：
Miwa, Satomi;Jow, Howsun;Baty, Karen;Johnson, Amy;Czapiewski, Rafal;Saretzki, Gabriele;Treumann, Achim;von Zglinicki, Thomas
线粒体功能是衰老过程的一个重要决定因素;然而，使长寿的线粒体特性还没有得到很好的理解。在这里，我们表明，线粒体复合物I的最佳组装预测小鼠的寿命。使用一个公正的高覆盖率高置信度的方法，我们表明，电子传递链蛋白，特别是基质臂亚基的复合物I，减少在年轻的长寿小鼠，这是与改善复合物I组装，更高的复合物I连接状态3耗氧率和减少超氧化物的产生，而相反的是在老年小鼠。复合物I组装的破坏降低了氧化代谢，伴随着线粒体超氧化物产生的增加。这是通过敲除线粒体伴侣抑制素来拯救的。破坏复合物I组装导致原代细胞过早衰老。我们提出，较低丰度的游离催化复合物I组分支持复合物I组装、底物利用的功效和最小的ROS产生，从而能够延长寿命。 线粒体与衰老有关，但它们究竟是如何参与的仍有争议。在这里，作者表明，线粒体复合物I的最佳组装预测小鼠的寿命，而部分复合物I组装增加了活性氧的产生。
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. Mitochondria are involved in ageing but exactly how they are involved is controversial. Here the authors show that optimal assembly of mitochondrial complex I predicts longevity in mice, whereas partial complex I assembly increases the production of reactive oxygen species.
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影响因子：
29
作者：
Balsa, Eduardo;Marco, Ricardo;Antonio Enriquez, Jose
通讯作者：
Antonio Enriquez, Jose
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
影响因子：
3.9
作者：
Chakravarti, Bulbul;Oseguera, Melva;Chakravarti, Deb N.
通讯作者：
Chakravarti, Deb N.
DOI：
10.1111/j.1532-5415.1972.tb00787.x
发表时间：
1972-01-01
影响因子：
6.3
作者：
HARMAN, D
通讯作者：
HARMAN, D
影响因子：
4.4
作者：
Craig, R;Cortens, JP;Beavis, RC
通讯作者：
Beavis, RC