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

• Published in: Biochemical and biophysical research communications Vol. 468; no. 4; pp. 807 - 812
• Main Authors: Liang, Lei, Li, Qingguo, Huang, Liyong, Li, Dawei, Li, Xinxiang
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 25.12.2015
• Subjects: Acetylation; Anion Transport Proteins - chemistry; Binding Sites; Cell growth; Computer Simulation; Enzyme Activation; Glucose - chemistry; HEK293 Cells; Humans; Mitochondrial Membrane Transport Proteins; Mitochondrial Proteins - chemistry; Models, Chemical; MPC1; Protein Binding; Sirt3; Sirtuin 3 - chemistry; Substrate Specificity; Sirt3; Cell growth; Acetylation; MPC1
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2015.11.036

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. •MPC1 is acetylated.•Sirt3 binds to and deacetylates MPC1.•High glucose decreases MPC1 acetylation level and increases Sirt3-MPC1 binding.•Acetylation of MPC1 inhibits its activity and abolishes its function in inhibition of colon cancer cell growth.