Mcp3 is a novel mitochondrial outer membrane protein that follows a unique IMP‐dependent biogenesis pathway

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.

Interaction network of the mitochondrial outer membrane protein Mcp3

“…In the same work, a role for Om45 in coordination of metabolite flux in and out of the organelle via porin channels in the MOM and transporter proteins of the carrier type in the MIM was proposed. Considering a possible involvement of Mcp3 in metabolite transport, we can speculate an alteration of metabolite flux of mitochondria could explain the capacity of high levels of Mcp3 to partially rescue the growth defect of ERMES deletion mutants . Yet, we did not observe a cross‐linking adduct of HA‐Mcp3 with Por1 (data not shown).…”

“…Recently, we identified Mcp3 as a novel MOM protein that partially rescues as an overexpression suppressor ERMES loss of function mutants and follows a unique import pathway . Although we could show that overexpression of Mcp3 in yeast cells lacking functional ERMES complex leads to partial restoration of mitochondrial morphology and lipid composition, the molecular function of Mcp3 in mitochondria is basically unknown.…”

“…We applied a functional HA‐tagged variant of Mcp3 to search for potential interactors. Crude mitochondria from mcp3 Δ cells with or without the HA‐tagged Mcp3, were lysed and incubated with anti‐HA beads for pull‐down analysis.…”

“…Recently, we identified three high‐copy suppressors of loss of ERMES, Mcp1‐3 . One of them, the MOM protein Mcp1 was shown to be involved in vacuole–mitochondria contacts .…”

“…Similar to ERMES subunits, Mcp1 does not have homologs in higher eukaryotes. Another suppressor is the MOM protein Mcp3 that follows a unique import pathway . Of note, the rescue capacity of Mcp3 for loss of ERMES is rather weak and like Mcp1 and ERMES, Mcp3 has no obvious homologs in higher eukaryotes.…”