title: Sirt3 binds to and deacetylates mitochondrial pyruvate carrier 1 to enhance its activity.
abstract: 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.
authors.affiliation: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, PR China.
authors.forename: Qingguo
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, PR China.
authors.forename: Liyong
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, PR China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, PR China. Electronic address: xinxianglics@gmail.com.
authors.forename: Xinxiang
authors.initials: X
authors.lastname: Li
mesh_terms: D000107:Acetylation; D027321:Anion Transport Proteins / Q000737:chemistry*; D001665:Binding Sites; D003198:Computer Simulation; D004789:Enzyme Activation; D005947:Glucose / Q000737:chemistry*; D057809:HEK293 Cells; D006801:Humans; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins / Q000737:chemistry*; D008956:Models, Chemical; D027501:Monocarboxylic Acid Transporters; D011485:Protein Binding; D056566:Sirtuin 3 / Q000737:chemistry*; D013379:Substrate Specificity
chemical_list: D027321:Anion Transport Proteins; C573718:MPC1 protein, human; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D027501:Monocarboxylic Acid Transporters; C466093:SIRT3 protein, human; D056566:Sirtuin 3; D005947:Glucose
keywords: Acetylation; Cell growth; MPC1; Sirt3