Role of the AAA protease Yme1 in folding of proteins in the intermembrane space of mitochondria

被引:49
作者
Schreiner, Bernadette [1 ]
Westerburg, Heike [1 ]
Forne, Ignasi [2 ]
Imhof, Axel [2 ]
Neupert, Walter [1 ,3 ]
Mokranjac, Dejana [1 ]
机构
[1] Univ Munich, Adolf Butenandt Inst, D-81377 Munich, Germany
[2] Univ Munich, Adolf Butenandt Inst, Zent Lab Prot Analyt, D-80336 Munich, Germany
[3] Max Planck Inst Biochem, D-82152 Martinsried, Germany
关键词
CYTOCHROME-C-OXIDASE; SACCHAROMYCES-CEREVISIAE; ENDOPLASMIC-RETICULUM; MOLECULAR CHAPERONES; YEAST MITOCHONDRIA; MEMBRANE ORGANIZATION; MASS-SPECTROMETRY; SUBSTRATE-BINDING; TIM23; COMPLEX; IMPORT MOTOR;
D O I
10.1091/mbc.E12-05-0420
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The vast majority of mitochondrial proteins are synthesized in the cytosol and transported into the organelle in a largely, if not completely, unfolded state. The proper function of mitochondria thus depends on folding of several hundreds of proteins in the various subcompartments of the organelle. Whereas folding of proteins in the mitochondrial matrix is supported by members of several chaperone families, very little is known about folding of proteins in the intermembrane space (IMS). We targeted dihydrofolate reductase (DHFR) as a model substrate to the IMS of yeast mitochondria and analyzed its folding. DHFR can fold in this compartment, and its aggregation upon heat shock can be prevented in an ATP-dependent manner. Yme1, an AAA (ATPases associated with diverse cellular activities) protease of the IMS, prevented aggregation of DHFR. Analysis of protein aggregates in mitochondria lacking Yme1 revealed the presence of a number of proteins involved in the establishment of mitochondrial ultrastructure, lipid metabolism, protein import, and respiratory growth. These findings explain the pleiotropic effects of deletion of YME1 and suggest an important role for Yme1 as a folding assistant, in addition to its proteolytic function, in the protein homeostasis of mitochondria
引用
收藏
页码:4335 / 4346
页数:12
相关论文
共 92 条
[1]   The TOM core complex: The general protein import pore of the outer membrane of mitochondria [J].
Ahting, U ;
Thun, C ;
Hegerl, R ;
Typke, D ;
Nargang, FE ;
Neupert, W ;
Nussberger, S .
JOURNAL OF CELL BIOLOGY, 1999, 147 (05) :959-968
[2]   TRAP-1, the mitochondrial Hsp90 [J].
Altieri, Dario C. ;
Stein, Gary S. ;
Lian, Jane B. ;
Languino, Lucia R. .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2012, 1823 (03) :767-773
[3]   Characterization of peptides released from mitochondria -: Evidence for constant proteolysis and peptide efflux [J].
Augustin, S ;
Nolden, M ;
Müller, S ;
Hardt, O ;
Arnold, I ;
Langer, T .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (04) :2691-2699
[4]   Mitochondrial protein quality control during biogenesis and aging [J].
Baker, Brooke M. ;
Haynes, Cole M. .
TRENDS IN BIOCHEMICAL SCIENCES, 2011, 36 (05) :254-261
[5]   Quality Control of Mitochondrial Proteostasis [J].
Baker, Michael J. ;
Tatsuta, Takashi ;
Langer, Thomas .
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY, 2011, 3 (07) :1-19
[6]   Adapting proteostasis for disease intervention [J].
Balch, William E. ;
Morimoto, Richard I. ;
Dillin, Andrew ;
Kelly, Jeffery W. .
SCIENCE, 2008, 319 (5865) :916-919
[7]   Molecular chaperone function of Mia40 triggers consecutive induced folding steps of the substrate in mitochondrial protein import [J].
Banci, Lucia ;
Bertini, Ivano ;
Cefaro, Chiara ;
Cenacchi, Lucia ;
Ciofi-Baffoni, Simone ;
Felli, Isabella Caterina ;
Gallo, Angelo ;
Gonnelli, Leonardo ;
Luchinat, Enrico ;
Sideris, Dionisia ;
Tokatlidis, Kostas .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (47) :20190-20195
[8]   Mitochondrial enzymes are protected from stress-induced aggregation by mitochondrial chaperones and the Pim1/LON protease [J].
Bender, Tom ;
Lewrenz, Ilka ;
Franken, Sebastian ;
Baitzel, Catherina ;
Voos, Wolfgang .
MOLECULAR BIOLOGY OF THE CELL, 2011, 22 (05) :541-554
[9]   Presequence-dependent folding ensures MrpL32 processing by the m-AAA protease in mitochondria [J].
Bonn, Florian ;
Tatsuta, Takashi ;
Petrungaro, Carmelina ;
Riemer, Jan ;
Langer, Thomas .
EMBO JOURNAL, 2011, 30 (13) :2545-2556
[10]   Molecular chaperones and protein quality control [J].
Bukau, Bernd ;
Weissman, Jonathan ;
Horwich, Arthur .
CELL, 2006, 125 (03) :443-451