Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, 1, 00133 Rome, Italy.
Curr Mol Med. 2013 Jan;13(1):140-54.
SIRT1 and PGC-1α are two nutrient sensing master regulators of cellular metabolism and their upregulation is often linked to increased lifespan. SIRT1 and PGC-1α modulate the expression of a set of nuclear genes controlling many metabolic pathways. In recent years mounting evidence has indicated the implication of these proteins in several mitochondrial diseases including neurodegenerative disorders, myopathies and Type II diabetes mellitus. Recently, these proteins have been localized in cytoplasm and mitochondria wherein they target novel substrates opening new insight into their possible function in modulating extranuclear genes and proteins. This review will firstly summarize the nuclear function of SIRT1 and PGC-1α. Then, data from papers demonstrating the presence of SIRT1 and PGC-1α in the cytoplasm and in mitochondria will be outlined so that these extranuclear forms do not remain out of sight. Finally, very recent evidence of the alteration of the pathways governed by SIRT1 and PGC-1α in human mitochondrial diseases will be described and the possible role of their mitochondrial forms will be briefly discussed.
SIRT1 和 PGC-1α 是两种营养感应的细胞代谢主调控因子，它们的上调通常与寿命的延长有关。SIRT1 和 PGC-1α 调节一组控制多种代谢途径的核基因的表达。近年来，越来越多的证据表明这些蛋白质与几种线粒体疾病有关，包括神经退行性疾病、肌病和 II 型糖尿病。最近，这些蛋白质已在细胞质和线粒体中定位，在那里它们针对新的底物，为它们在调节核外基因和蛋白质方面的可能功能提供了新的见解。本综述将首先总结 SIRT1 和 PGC-1α 的核功能。然后，将概述表明 SIRT1 和 PGC-1α 存在于细胞质和线粒体中的文献数据，以便这些核外形式不会被忽视。最后，将描述人类线粒体疾病中 SIRT1 和 PGC-1α 调控途径改变的最新证据，并简要讨论其线粒体形式的可能作用。
