Identification and Functional Expression of the Mitochondrial Pyruvate Carrier

被引:639
作者
Herzig, Sebastien [1 ]
Raemy, Etienne [1 ]
Montessuit, Sylvie [1 ]
Veuthey, Jean-Luc [2 ]
Zamboni, Nicola [3 ]
Westermann, Benedikt [4 ]
Kunji, Edmund R. S. [5 ]
Martinou, Jean-Claude [1 ]
机构
[1] Univ Geneva, Dept Cell Biol, CH-1211 Geneva 4, Switzerland
[2] Univ Geneva, Sch Pharmaceut Sci, CH-1211 Geneva 4, Switzerland
[3] Inst Mol Syst Biol, CH-8093 Zurich, Switzerland
[4] Univ Bayreuth, D-95440 Bayreuth, Germany
[5] MRC, Mitochondria Biol Unit, Cambridge CB2 0XY, England
基金
瑞士国家科学基金会;
关键词
SACCHAROMYCES-CEREVISIAE; LIPOIC ACID; LACTOCOCCUS-LACTIS; DEHYDROGENASE; SPECIFICITY; CATABOLISM; TRANSPORT; MEMBRANE;
D O I
10.1126/science.1218530
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
The transport of pyruvate, the end product of glycolysis, into mitochondria is an essential process that provides the organelle with a major oxidative fuel. Although the existence of a specific mitochondrial pyruvate carrier (MPC) has been anticipated, its molecular identity remained unknown. We report that MPC is a heterocomplex formed by two members of a family of previously uncharacterized membrane proteins that are conserved from yeast to mammals. Members of the MPC family were found in the inner mitochondrial membrane, and yeast mutants lacking MPC proteins showed severe defects in mitochondrial pyruvate uptake. Coexpression of mouse MPC1 and MPC2 in Lactococcus lactis promoted transport of pyruvate across the membrane. These observations firmly establish these proteins as essential components of the MPC.
引用
收藏
页码:93 / 96
页数:4
相关论文
共 17 条
[1]
A Mitochondrial Pyruvate Carrier Required for Pyruvate Uptake in Yeast, Drosophila, and Humans [J].
Bricker, Daniel K. ;
Taylor, Eric B. ;
Schell, John C. ;
Orsak, Thomas ;
Boutron, Audrey ;
Chen, Yu-Chan ;
Cox, James E. ;
Cardon, Caleb M. ;
Van Vranken, Jonathan G. ;
Dephoure, Noah ;
Redin, Claire ;
Boudina, Sihem ;
Gygi, Steven P. ;
Brivet, Michele ;
Thummel, Carl S. ;
Rutter, Jared .
SCIENCE, 2012, 337 (6090) :96-100
[2]
Proteomic analysis of the mouse liver mitochondrial inner membrane [J].
Da Cruz, S ;
Xenarios, I ;
Langridge, J ;
Vilbois, F ;
Parone, PA ;
Martinou, JC .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (42) :41566-41571
[3]
DICKINSON JR, 1986, MOL GEN GENET, V204, P103
[4]
THE CATABOLISM OF BRANCHED-CHAIN AMINO-ACIDS OCCURS VIA 2-OXOACID DEHYDROGENASE IN SACCHAROMYCES-CEREVISIAE [J].
DICKINSON, JR ;
DAWES, IW .
JOURNAL OF GENERAL MICROBIOLOGY, 1992, 138 :2029-2033
[5]
SPECIFICITY AND METABOLIC IMPLICATIONS OF INHIBITION OF PYRUVATE TRANSPORT IN ISOLATED-MITOCHONDRIA AND INTACT TISSUE PREPARATIONS BY ALPHA-CYANO-4-HYDROXYCINNAMATE AND RELATED COMPOUNDS [J].
HALESTRAP, AP ;
DENTON, RM .
BIOCHEMICAL JOURNAL, 1975, 148 (01) :97-106
[6]
MITOCHONDRIAL PYRUVATE CARRIER - KINETICS AND SPECIFICITY FOR SUBSTRATES AND INHIBITORS [J].
HALESTRAP, AP .
BIOCHEMICAL JOURNAL, 1975, 148 (01) :85-96
[7]
Overview of the molecular and biochemical basis of branched-chain amino acid catabolism [J].
Harris, RA ;
Joshi, M ;
Jeoung, NH ;
Obayashi, M .
JOURNAL OF NUTRITION, 2005, 135 (06) :1527S-1530S
[8]
Mitochondrial fatty acid synthesis - An adopted set of enzymes making a pathway of major importance for the cellular metabolism [J].
Hiltunen, J. Kalervo ;
Chen, Zhijun ;
Haapalainen, Antti M. ;
Wierenga, Rik K. ;
Kastaniotis, Alexander J. .
PROGRESS IN LIPID RESEARCH, 2010, 49 (01) :27-45
[9]
HFA1 encoding an organelle-specific acetyl-CoA carboxylase controls mitochondrial fatty acid synthesis in Saccharomyces cerevisiae [J].
Hoja, U ;
Marthol, S ;
Hofmann, J ;
Stegner, S ;
Schulz, R ;
Meier, S ;
Greiner, E ;
Schweizer, E .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (21) :21779-21786
[10]
Selective inactivation of α-ketoglutarate dehydrogenase and pyruvate dehydrogenase:: Reaction of lipoic acid with 4-hydroxy-2-nonenal [J].
Humphries, KM ;
Szweda, LI .
BIOCHEMISTRY, 1998, 37 (45) :15835-15841