Proteomic analysis of the mouse liver mitochondrial inner membrane

被引:206
作者
Da Cruz, S
Xenarios, I
Langridge, J
Vilbois, F
Parone, PA
Martinou, JC
机构
[1] Univ Geneva, Dept Cellular Biol, CH-1205 Geneva, Switzerland
[2] Serono Int SA, Serono Pharmaceut Res Inst, CH-1228 Geneva, Switzerland
[3] Micromass UK Ltd, Manchester M23 9LZ, Lancs, England
关键词
D O I
10.1074/jbc.M304940200
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
Mitochondria play a crucial role in cellular homeostasis, which justifies the increasing interest in mapping the different components of these organelles. Here we have focused our study on the identification of proteins of the mitochondrial inner membrane (MIM). This membrane is of particular interest because, besides the well known components of the respiratory chain complexes, it contains several ion channels and many carrier proteins that certainly play a key role in mitochondrial function and, therefore, deserve to be identified at the molecular level. To achieve this goal we have used a novel approach combining the use of highly purified mouse liver mitochondrial inner membranes, extraction of membrane proteins with organic acid, and two-dimensional liquid chromatography coupled to tandem mass spectrometry. This procedure allowed us to identify 182 proteins that are involved in several biochemical processes, such as the electron transport machinery, the protein import machinery, protein synthesis, lipid metabolism, and ion or substrate transport. The full range of isoelectric point (3.9-12.5), molecular mass ( 6 527 kDa), and hydrophobicity values ( up to 16 transmembrane predicted domains) were represented. In addition, of the 182 proteins found, 20 were unknown or had never previously been associated with the MIM. Overexpression of some of these proteins in mammalian cells confirmed their mitochondrial localization and resulted in severe remodeling of the mitochondrial network. This study provides the first proteome of the MIM and provides a basis for a more detailed study of the newly characterized proteins of this membrane.
引用
收藏
页码:41566 / 41571
页数:6
相关论文
共 28 条
[1]   MOSC domains: ancient, predicted sulfur-carrier domains, present in diverse metal-sulfur cluster biosynthesis proteins including Molybdenum cofactor sulfurases [J].
Anantharaman, V ;
Aravind, L .
FEMS MICROBIOLOGY LETTERS, 2002, 207 (01) :55-61
[2]  
Barnes TM, 1996, J NEUROCHEM, V67, P46
[3]   Mitochondrial intermembrane junctional complexes and their involvement in cell death [J].
Crompton, M ;
Barksby, E ;
Johnson, N ;
Capano, M .
BIOCHIMIE, 2002, 84 (2-3) :143-152
[4]  
Fountoulakis M, 2002, ELECTROPHORESIS, V23, P311, DOI 10.1002/1522-2683(200202)23:2<311::AID-ELPS311>3.0.CO
[5]  
2-0
[6]   The mitochondrial K-ATP channel as a receptor for potassium channel openers [J].
Garlid, KD ;
Paucek, P ;
YarovYarovoy, V ;
Sun, XC ;
Schindler, PA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (15) :8796-8799
[7]   MEC-2 regulates C-elegans DEG/ENaC channels needed for mechanosensation [J].
Goodman, MB ;
Ernstrom, GG ;
Chelur, DS ;
O'Hagan, R ;
Yao, CA ;
Chalfie, M .
NATURE, 2002, 415 (6875) :1039-1042
[8]   Rat liver mitochondrial contact sites and carnitine palmitoyltransferase-I [J].
Hoppel, C ;
Kerner, J ;
Turkaly, P ;
Tandler, B .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2001, 392 (02) :321-325
[9]   Systematic functional analysis of the Caenorhabditis elegans genome using RNAi [J].
Kamath, RS ;
Fraser, AG ;
Dong, Y ;
Poulin, G ;
Durbin, R ;
Gotta, M ;
Kanapin, A ;
Le Bot, N ;
Moreno, S ;
Sohrmann, M ;
Welchman, DP ;
Zipperlen, P ;
Ahringer, J .
NATURE, 2003, 421 (6920) :231-237
[10]   Empirical statistical model to estimate the accuracy of peptide identifications made by MS/MS and database search [J].
Keller, A ;
Nesvizhskii, AI ;
Kolker, E ;
Aebersold, R .
ANALYTICAL CHEMISTRY, 2002, 74 (20) :5383-5392