Mitochondrial sirtuins in the regulation of mitochondrial activity and metabolic adaptation.
Mitochondrial sirtuins in the regulation of mitochondrial activity and metabolic adaptation.
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DOI：
10.1007/978-3-642-21631-2_8
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发表时间：
2011
影响因子：
--
通讯作者：
Bao, Jianjun
中科院分区：
文献类型：
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作者：
Lombard, David B;Tishkoff, Daniel X;Bao, Jianjun
在真核生物中，线粒体执行许多对细胞和生物体健康至关重要的功能。线粒体的活动如何在不同的环境条件下进行调节，例如饮食的变化，仍然是生物学中一个重要的未解决的问题。在这里，我们审查新出现的证据表明，可逆乙酰化的线粒体蛋白质的赖氨酸残基是一个关键的机制，线粒体功能进行调整，以满足环境的需求。在哺乳动物中，NAD+依赖性脱乙酰酶的sirtuin类的三个成员-SIRT 3、SIRT 4和SIRT 5-定位于线粒体并调节参与多种生化途径的靶标。最近对SIRT 3的研究强调了这种活性的重要性，表明这种蛋白质抑制了多种与年龄相关的病理学的出现：听力损失，心脏纤维化和恶性肿瘤。总之，这些发现表明，线粒体蛋白乙酰化是哺乳动物调节线粒体功能以维持细胞和生物体内平衡的一种重要手段。
In eukaryotes, mitochondria carry out numerous functions central to cellular and organismal health. How mitochondrial activities are regulated in response to differing environmental conditions, such as variations in diet, remains an important unsolved question in biology. Here we review emerging evidence suggesting that reversible acetylation of mitochondrial proteins on lysine residues represents a key mechanism by which mitochondrial functions are adjusted to meet environmental demands. In mammals, three members of the sirtuin class of NAD+-dependent deacetylases – SIRT3, SIRT4, and SIRT5 – localize to mitochondria and regulate targets involved in a diverse array of biochemical pathways. The importance of this activity is highlighted by recent studies of SIRT3 indicating that this protein suppresses the emergence of diverse age-related pathologies: hearing loss, cardiac fibrosis, and malignancy. Together, these findings argue that mitochondrial protein acetylation represents a central means by which mammals regulate mitochondrial functions to maintain cellular and organismal homeostasis.