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Mol Cell. 2014 Dec 4;56(5):641-52. doi: 10.1016/j.molcel.2014.10.010. Epub 2014 Nov 13.

Mgr2 functions as lateral gatekeeper for preprotein sorting in the mitochondrial inner membrane.

Author information

1
Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany.
2
Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany; Fakultät für Biologie, Universität Freiburg, 79104 Freiburg, Germany.
3
Centre de Génétique Moléculaire, CNRS, 91190 Gif-sur-Yvette, France.
4
Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, Universität Freiburg, 79104 Freiburg, Germany.
5
International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland.
6
Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, Universität Freiburg, 79104 Freiburg, Germany. Electronic address: nikolaus.pfanner@biochemie.uni-freiburg.de.
7
Institut für Biochemie und Molekularbiologie, ZBMZ, Universität Freiburg, 79104 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, Universität Freiburg, 79104 Freiburg, Germany. Electronic address: martin.van.der.laan@biochemie.uni-freiburg.de.

Abstract

The majority of preproteins destined for mitochondria carry N-terminal presequences. The presequence translocase of the inner mitochondrial membrane (TIM23 complex) plays a central role in protein sorting. Preproteins are either translocated through the TIM23 complex into the matrix or are laterally released into the inner membrane. We report that the small hydrophobic protein Mgr2 controls the lateral release of preproteins. Mgr2 interacts with preproteins in transit through the TIM23 complex. Overexpression of Mgr2 delays preprotein release, whereas a lack of Mgr2 promotes preprotein sorting into the inner membrane. Preproteins with a defective inner membrane sorting signal are translocated into the matrix in wild-type mitochondria but are released into the inner membrane in Mgr2-deficient mitochondria. We conclude that Mgr2 functions as a lateral gatekeeper of the mitochondrial presequence translocase, providing quality control for the membrane sorting of preproteins.

PMID:
25454944
DOI:
10.1016/j.molcel.2014.10.010
[Indexed for MEDLINE]
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