The coordination of nuclear and mitochondrial communication during aging and calorie restriction.
The coordination of nuclear and mitochondrial communication during aging and calorie restriction.
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DOI：
10.1016/j.arr.2009.03.003
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发表时间：
2009-07
影响因子：
13.1
通讯作者：
Haigis MC
中科院分区：
文献类型：
--
作者：
Finley LW;Haigis MC
线粒体是整合环境信号以调节能量产生、细胞凋亡和Ca 2+稳态的动态细胞器。毫不奇怪，线粒体功能障碍与衰老和年龄相关疾病中观察到的病理学有关。绝大多数线粒体蛋白质在核基因组中编码，因此细胞核和线粒体之间的通信对于维持适当的线粒体功能至关重要。几种蛋白质已经成为线粒体基因表达的主要调节因子，能够响应细胞的生理需求增加线粒体基因的转录。本文就PGC-1α、SIRT 1、AMPK和mTOR等蛋白质对线粒体功能的调节及其在衰老、热量限制和年龄相关疾病中的作用进行综述。我们还将讨论线粒体向细胞核发出信号的途径。虽然这种逆行信号在哺乳动物中没有得到很好的研究，但越来越多的证据表明，它可能是未来衰老研究的一个重要领域。对线粒体和细胞核通讯机制的更深入了解将有助于减缓或逆转衰老过程中发生的线粒体功能障碍。
Mitochondria are dynamic organelles that integrate environmental signals to regulate energy production, apoptosis and Ca2+ homeostasis. Not surprisingly mitochondrial dysfunction is associated with aging and the pathologies observed in age-related diseases. The vast majority of mitochondrial proteins are encoded in the nuclear genome, and so communication between the nucleus and mitochondria is essential for maintenance of appropriate mitochondrial function. Several proteins have emerged as major regulators of mitochondrial gene expression, capable of increasing transcription of mitochondrial genes in response to the physiological demands of the cell. In this review, we will focus on PGC-1α, SIRT1, AMPK and mTOR and discuss how these proteins regulate mitochondrial function and their potential involvement in aging, calorie restriction and age-related disease. We will also discuss the pathways through which mitochondria signal to the nucleus. Although such retrograde signaling is not well studied in mammals, there is growing evidence to suggest that it may be an important area for future aging research. Greater understanding of the mechanisms by which mitochondria and the nucleus communicate will facilitate efforts to slow or reverse the mitochondrial dysfunction that occurs during aging.