Oma1, a novel membrane-bound metallopeptidase in mitochondria with activities overlapping with the m-AAA protease

被引:123
作者
Käser, M [1 ]
Kambacheld, M [1 ]
Kisters-Woike, B [1 ]
Langer, T [1 ]
机构
[1] Univ Cologne, Inst Genet, D-50674 Cologne, Germany
关键词
D O I
10.1074/jbc.M305584200
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
The integrity of the inner membrane of mitochondria is maintained by a membrane-embedded quality control system that ensures the removal of misfolded membrane proteins. Two ATP-dependent AAA proteases with catalytic sites at opposite membrane surfaces are key components of this proteolytic system. Here we describe the identification of a novel conserved metallopeptidase that exerts activities overlapping with the m-AAA protease and was therefore termed Oma1. Both peptidases are integral parts of the inner membrane and mediate the proteolytic breakdown of a misfolded derivative of the polytopic inner membrane protein Oxa1. The m-AAA protease cleaves off the matrix-exposed C-terminal domain of Oxa1 and processively degrades its transmembrane domain. In the absence of the m-AAA protease, proteolysis of Oxa1 is mediated in an ATP-independent manner by Oma1 and a yet unknown peptidase resulting in the accumulation of N- and C-terminal proteolytic fragments. Oma1 exposes its proteolytic center to the matrix side; however, mapping of Oma1 cleavage sites reveals clipping of Oxa1 in loop regions at both membrane surfaces. These results identify Oma1 as a novel component of the quality control system in the inner membrane of mitochondria. Proteins homologous to Oma1 are present in higher eukaryotic cells, eubacteria and archaebacteria, suggesting that Oma1 is the founding member of a conserved family of membrane-embedded metallopeptidases.
引用
收藏
页码:46414 / 46423
页数:10
相关论文
共 56 条
  • [11] A novel two-step mechanism for removal of a mitochondrial signal sequence involves the mAAA complex and the putative rhomboid protease Pcp1
    Esser, K
    Tursun, B
    Ingenhoven, M
    Michaelis, G
    Pratje, E
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 2002, 323 (05) : 835 - 843
  • [12] Mitochondrial processing peptidases
    Gakh, E
    Cavadini, P
    Isaya, G
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2002, 1592 (01): : 63 - 77
  • [13] Plant mitochondria contain proteolytic and regulatory subunits of the ATP-dependent Clp protease
    Halperin, T
    Zheng, B
    Itzhaki, H
    Clarke, AK
    Adam, Z
    [J]. PLANT MOLECULAR BIOLOGY, 2001, 45 (04) : 461 - 468
  • [14] Hereditary spastic paraplegia SPG13 is associated with a mutation in the gene encoding the mitochondrial chaperonin Hsp60
    Hansen, JJ
    Dürr, A
    Cournu-Rebeix, I
    Georgopoulos, C
    Ang, D
    Nielsen, MN
    Davoine, CS
    Brice, A
    Fontaine, B
    Gregersen, N
    Bross, P
    [J]. AMERICAN JOURNAL OF HUMAN GENETICS, 2002, 70 (05) : 1328 - 1332
  • [15] Oxa1p acts as a general membrane insertion machinery for proteins encoded by mitochondrial DNA
    Hell, K
    Neupert, W
    Stuart, RA
    [J]. EMBO JOURNAL, 2001, 20 (06) : 1281 - 1288
  • [16] Processing of Mgm1 by the rhomboid-type protease Pcp1 is required for maintenance of mitochondrial morphology and of mitochondrial DNA
    Herlan, M
    Vogel, F
    Bornhövd, C
    Neupert, W
    Reichert, AS
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (30) : 27781 - 27788
  • [17] Herrmann J.M., 1994, CELL BIOL, P538
  • [18] Insertion into the mitochondrial inner membrane of a polytopic protein, the nuclear-encoded Oxa1p
    Herrmann, JM
    Neupert, W
    Stuart, RA
    [J]. EMBO JOURNAL, 1997, 16 (09) : 2217 - 2226
  • [19] Functional proteolytic complexes of the human mitochondrial ATP-dependent protease, hClpXP
    Kang, SG
    Ortega, J
    Singh, SK
    Wang, N
    Huang, NN
    Steven, AC
    Maurizi, MR
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (23) : 21095 - 21102
  • [20] Protein degradation in mitochondria
    Käser, M
    Langer, T
    [J]. SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, 2000, 11 (03) : 181 - 190