线粒体去乙酰化酶SIRT3与衰老疾病

线粒体去乙酰化酶SIRT3是酵母Sir2同源蛋白,通过对线粒体多种蛋白质赖氨酸的去乙酰化修饰,它可以调控多种代谢过程,如脂肪酸的β-氧化作用、TCA循环、氧化磷酸化等.SIRT3可参与氧化应激反应,降低细胞内ROS水平;也可以作为一种肿瘤抑制因子,促进细胞的凋亡.在某些乳腺癌细胞中,SIRT3表达下调.敲除SIRT3或者SIRT3表达降低,可影响与代谢相关的衰老性疾病如心脏疾病、癌症等的发生.论文总结了近年去乙酰化酶SIRT3在代谢调控及癌症细胞凋亡中的分子机制以及SIRT3与心脏疾病、癌症的相互关系,希望为衰老疾病的预防和治疗提供一定的理论基础.

Mitochondrial Deacetylase SIRT3 and the Aging-related Diseases

Mitochondrial deacetylase SIRT3 is the homolog of yeast Sir2 and it can modulate diverse mitochondria-localized processes such as fatty acid β-oxidation, tricarboxylic acid （TCA） cycle and oxidative phosphorylation by deacetylation of the targeted lysine on the mitochondrial proteins. Furthermore, SIRT3 is involved in oxidative stress and reduces the cellular ROS level. SIRT3 also acts as a tumor suppressor to induce cancer cell apoptosis. In some breast carcinoma, the expression level of SIRT3 is down-regulated. Deletion or downregulation of SIRT3 in animal model promotes the onset of metabolic aging-related diseases, such as heart failure and cancer. In this review, we summarized the current evidences of deacetylase SIRT3 and the involved regulatory mechanism in metabolism and cancer cell apoptosis, and the correlation between heart failure, cancer with deacetylase SIRT3. It aims to provide some novel insights for prevention and treatment of the aging-related diseases.