Mcp3 is a novel mitochondrial outer membrane protein that follows a unique IMP‐dependent biogenesis pathway. (25th May 2016)

• Record Type: Journal Article
• Authors: Sinzel, Monika; Tan, Tao; Wendling, Philipp; Kalbacher, Hubert; Özbalci, Cagakan; Chelius, Xenia; Westermann, Benedikt; Brügger, Britta; Rapaport, Doron; Dimmer, Kai Stefan
• Is Part Of: EMBO reports. Volume 17:Number 7(2016:Jul.)
• Page Start: 965
• Page End: 981
• Publication Date: 2016-05-25
• Subjects: ERMES complex -- IMP -- Mdm10 -- mitochondria -- outer membrane; Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.15252/embr.201541273
• Languages: English
• ISSNs: 1469-221X

Abstract

Abstract: Mitochondria are separated from the remainder of the eukaryotic cell by the mitochondrial outer membrane (MOM). The MOM plays an important role in different transport processes like lipid trafficking and protein import. In yeast, the ER–mitochondria encounter structure (ERMES) has a central, but poorly defined role in both activities. To understand the functions of the ERMES, we searched for suppressors of the deficiency of one of its components, Mdm10, and identified a novel mitochondrial protein that we named Mdm10 complementing protein 3 (Mcp3). Mcp3 partially rescues a variety of ERMES‐related phenotypes. We further demonstrate that Mcp3 is an integral protein of the MOM that follows a unique import pathway. It is recognized initially by the import receptor Tom70 and then crosses the MOM via the translocase of the outer membrane. Mcp3 is next relayed to the TIM23 translocase at the inner membrane, gets processed by the inner membrane peptidase (IMP) and finally integrates into the MOM. Hence, Mcp3 follows a novel biogenesis route where a MOM protein is processed by a peptidase of the inner membrane. Synopsis: This study reports that the mitochondrial outer membrane protein Mcp3 is a suppressor of deficiencies in ERMES complex components that cause loss of ER–mitochondria contacts. Mcp3 follows a novel and unique import pathway, which includes processing by the inner membrane peptidase IMP. Mcp3 partially rescues the loss of ERMES complex subunits. The mitochondrial outer membrane protein Mcp3 contains an N‐terminal targeting sequence and its import into the organelle requires membrane potential. Mcp3 is the first known mitochondrial outer membrane protein processed by a peptidase inside mitochondria. Abstract : This study reports that the mitochondrial outer membrane protein Mcp3 is a suppressor of deficiencies in ERMES complex components that cause loss of ER‐mitochondria contacts. Mcp3 follows a novel and unique import pathway, which includes processing by the inner membrane peptidase IMP.