Dynamic regulation of PGC-1alpha localization and turnover implicates mitochondrial adaptation in calorie restriction and the stress response.
Dynamic regulation of PGC-1alpha localization and turnover implicates mitochondrial adaptation in calorie restriction and the stress response.
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PGC-1Alpha定位和周转的动态调节暗示卡路里限制和应力反应中的线粒体适应性。
DOI：
10.1111/j.1474-9726.2007.00357.x
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发表时间：
2008-01
期刊：
影响因子：
7.8
通讯作者：
Weindruch, Richard
中科院分区：
文献类型：
--
作者：
Anderson, Rozalyn M.;Barger, Jamie L.;Edwards, Michael G.;Braun, Kristina H.;O'Connor, Clare E.;Prolla, Tomas A.;Weindruch, Richard
越来越多的证据表明长寿和抗应激能力是相关的，但其机制尚不清楚。我们报道了线粒体对氧化应激和热量限制的反应是通过一种涉及过氧化物酶体增殖物激活受体-γ共激活因子1α（PGC-1α）的共同机制来调节的。我们证明PGC-1α的亚细胞分布受到调节，其转录活性通过SIRT 1依赖的核积累而得到促进。此外，PGC-1α活性的持续时间受糖原合成酶激酶β（GSK 3 β）调节，GSK 3 β靶向PGC-1α进行核内蛋白酶体降解。这种调节机制允许独立控制PGC-1α激活的快速性和持续性。我们提供的证据表明，这种PGC-1α调节途径在小鼠体内发生，无论是在氧化应激反应中还是在热量限制下。我们的数据显示了线粒体功能如何适应外部刺激，并支持这样的适应是至关重要的参与细胞存活和通过热量限制延长寿命的概念。
There is increasing evidence that longevity and stress resistance are connected, but the mechanism is unclear. We report that mitochondria are regulated in response to oxidative stress and calorie restriction through a shared mechanism involving peroxisome proliferator-activated receptor-γ co-activator 1α (PGC-1α). We demonstrate that PGC-1α subcellular distribution is regulated, and its transcriptional activity is promoted through SIRT1-dependent nuclear accumulation. In addition, the duration of PGC-1α activity is regulated by glycogen synthase kinase beta (GSK3β), which targets PGC-1α for intranuclear proteasomal degradation. This mechanism of regulation permits the rapidity and persistence of PGC-1α activation to be independently controlled. We provide evidence that this pathway of PGC-1α regulation occurs in vivo in mice, both in the oxidative stress response and with calorie restriction. Our data show how mitochondrial function may be adapted in response to external stimuli, and support the concept that such adaptation is critically involved in cellular survival and in lifespan extension by calorie restriction.
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影响因子：
16
作者：
Avalos, JL;Bever, KM;Wolberger, C
通讯作者：
Wolberger, C
影响因子：
64.5
作者：
Lin, JD;Wu, PH;Spiegelman, BM
通讯作者：
Spiegelman, BM
DOI：
10.1093/gerona/61.7.675
发表时间：
2006-07-01
影响因子：
5.1
作者：
Baker, David J.;Betik, Andrew C.;Hepple, Russell T.
通讯作者：
Hepple, Russell T.
影响因子：
64.8
作者：
Baur, Joseph A.;Pearson, Kevin J.;Sinclair, David A.
通讯作者：
Sinclair, David A.
影响因子：
11.4
作者：
Aberle, H;Bauer, A;Kemler, R
通讯作者：
Kemler, R