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Regulation of mitochondrial phospholipids by Ups1/PRELI‐like proteins depends on proteolysis and Mdm35
Author(s) -
Potting Christoph,
Wilmes Claudia,
Engmann Tanja,
Osman Christof,
Langer Thomas
Publication year - 2010
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2010.169
Subject(s) - intermembrane space , cardiolipin , biology , proteolysis , mitochondrial intermembrane space , phosphatidylethanolamine , mitochondrial carrier , microbiology and biotechnology , biochemistry , inner mitochondrial membrane , mitochondrion , protease , translocase of the inner membrane , phospholipid , mitochondrial membrane transport protein , bacterial outer membrane , enzyme , membrane , phosphatidylcholine , gene , escherichia coli
The mitochondrial phospholipid metabolism critically depends on members of the conserved Ups1/PRELI‐like protein family in the intermembrane space. Ups1 and Ups2 (also termed Gep1) were shown to regulate the accumulation of cardiolipin (CL) and phosphatidylethanolamine (PE), respectively, in a lipid‐specific but coordinated manner. It remained enigmatic, however, how the relative abundance of both phospholipids in mitochondrial membranes is adjusted on the molecular level. Here, we describe a novel regulatory circuit determining the accumulation of Ups1 and Ups2 in the intermembrane space. Ups1 and Ups2 are intrinsically unstable proteins, which are degraded by distinct mitochondrial peptidases. The turnover of Ups2 is mediated by the i ‐AAA protease Yme1, whereas Ups1 is degraded by both Yme1 and the metallopeptidase Atp23. We identified Mdm35, a member of the twin Cx 9 C protein family, as a novel interaction partner of Ups1 and Ups2. Binding to Mdm35 ensures import and protects both proteins against proteolysis. Homologues to all components of this pathway are present in higher eukaryotes, suggesting that the regulation of mitochondrial CL and PE levels is conserved in evolution.