Sirt3 binds to and deacetylates mitochondrial pyruvate carrier 1 to enhance its activity

被引：42

作者：

Liang, Lei ^{[1
,2
]}

Li, Qingguo ^{[1
,2
]}

Huang, Liyong ^{[1
,2
]}

Li, Dawei ^{[1
,2
]}

Li, Xinxiang ^{[1
,2
]}

机构：

[1] Fudan Univ, Dept Colorectal Surg, Shanghai Canc Ctr, Shanghai 200032, Peoples R China

[2] Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai 200032, Peoples R China

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2015年 / 468卷 / 04期

关键词：

MPC1; Sirt3; Acetylation; Cell growth; C-MYC; ACETYLATION; METABOLISM; INHIBITION; TRANSPORT; KINASE; YEAST;

D O I：

10.1016/j.bbrc.2015.11.036

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Mitochondrial pyruvate carrier (MPC), composed of MPC1 and MPC2, can modulate pyruvate oxidation in mitochondrial and MPC1 expression correlates with poor prognosis of multiple cancers. Here, we reported that MPC1 is acetylated and its main acetylation sites are: K45 and K46. Sirt3 binds to and deacetylates MPC1. High glucose decreases MPC1 acetylation level by increasing Sirt3-MPC1 binding. Furthermore, acetylation mimic mutation of MPC1 reduces it activity and abolishes its function in inhibition of colon cancer cell growth. These results reveal a novel post-translational regulation of MPC1 by Sirt3, which is important for its activity and colon cancer cell growth. (C) 2015 Elsevier Inc. All rights reserved.

引用

页码：807 / 812

页数：6

共 26 条

[1] Mechanism of sirtuin inhibition by nicotinamide:: Altering the NAD+ cosubstrate specificity of a Sir2 enzyme [J].