4.7 Article

SIRT5 is under the control of PGC-1α and AMPK and is involved in regulation of mitochondrial energy metabolism

期刊

FASEB JOURNAL
卷 28, 期 7, 页码 3225-3237

出版社

WILEY
DOI: 10.1096/fj.13-245241

关键词

metformin; ATP; ERR alpha; PPAR alpha

资金

  1. Finnish Diabetes Research Foundation
  2. Diabetes Wellness Finland
  3. Research Council for Health of the Academy of Finland [138566]
  4. Academy of Finland (AKA) [138566, 138566] Funding Source: Academy of Finland (AKA)

向作者/读者索取更多资源

The sirtuins (SIRTs; SIRT1-7) are a family of NAD(+)-dependent enzymes that dynamically regulate cellular physiology. Apart from SIRT1, the functions and regulatory mechanisms of the SIRTs are poorly defined. We explored regulation of the SIRT family by 2 energy metabolism-controlling factors: peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1 alpha) and AMP-activated protein kinase (AMPK). Overexpression of PGC-1 alpha in mouse primary hepatocytes increased SIRT5 mRNA expression 4-fold and also the protein in a peroxisome proliferator-activated receptor alpha (PPAR alpha)-and estrogen-related receptor alpha (ERR alpha)-dependent manner. Furthermore, food withdrawal increased SIRT5 mRNA 1.3-fold in rat liver. Overexpression of AMPK in mouse hepatocytes increased expression of SIRT1, SIRT2, SIRT3, and SIRT6 <2-fold. In contrast, SIRT5 mRNA was down-regulated by 58%. The antidiabetes drug metformin (1 mM), an established AMPK activator, reduced the mouse SIRT5 protein level by 44% in cultured hepatocytes and by 31% in liver in vivo (300 mg/kg, 7 d). Metformin also induced hypersuccinylation of mitochondrial proteins. Moreover, SIRT5 overexpression increased ATP synthesis and oxygen consumption in HepG2 cells, but did not affect mitochondrial biogenesis. In summary, our results identified SIRT5 as a novel factor that controls mitochondrial function. Moreover, SIRT5 levels are regulated by PGC-1 alpha and AMPK, which have opposite effects on its expression.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据