Mitochondrial inner membrane protease promotes assembly of presequence translocase by removing a carboxy-terminal targeting sequence

被引：0
作者：
Raffaele Ieva
Anna K. Heißwolf
Michael Gebert
F.-Nora Vögtle
Florian Wollweber
Carola S. Mehnert
Silke Oeljeklaus
Bettina Warscheid
Chris Meisinger
Martin van der Laan
Nikolaus Pfanner
机构：
[1] Institut für Biochemie und Molekularbiologie,
[2] ZBMZ,undefined
[3] Universität Freiburg,undefined
[4] Faculty of Biology,undefined
[5] Universität Freiburg,undefined
[6] BIOSS Centre for Biological Signalling Studies,undefined
[7] Universität Freiburg,undefined
[8] Institut für Biologie II,undefined
[9] Fakultät für Biologie,undefined
[10] Funktionelle Proteomik,undefined
[11] Universität Freiburg,undefined
[12] Collaborative Research Centre for Functional Specificity,undefined
[13] Universität Freiburg,undefined
[14] Present address: Roche Diagnostics,undefined
[15] Pharma Research and Early Development,undefined
[16] 82377 Penzberg,undefined
[17] Germany,undefined
[18] Present address: Harvard Medical School,undefined
[19] Department of Neurobiology,undefined
[20] Boston,undefined
[21] Massachusetts 02115,undefined
[22] USA,undefined
来源：
Nature Communications | / 4卷
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摘要：
The presequence translocase of the inner mitochondrial membrane (TIM23 complex) is essential for importing cleavable preproteins into mitochondria. The preproteins contain amino-terminal targeting sequences that are removed by the mitochondrial processing peptidase (MPP). Some preproteins carry bipartite presequences that are cleaved twice, by MPP and the inner membrane protease (IMP). Here, we report that the TIM23 complex is altered in mitochondria lacking the IMP subunit Imp1 although none of the TIM23 components contains a bipartite presequence. We show that the TIM23 subunit Mgr2 is processed by IMP, but not by MPP. The cytosolic precursor of Mgr2 contains a carboxy-terminal sequence that promotes targeting to mitochondria, but impairs stable assembly and function of the mature TIM23 complex. IMP removes the carboxy-terminal targeting sequence and thus promotes proper assembly of the TIM23 complex. Our results reveal carboxy-terminal processing as a new mechanism in the biogenesis of the mitochondrial inner membrane.
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