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Mdm35p imports Ups proteins into the mitochondrial intermembrane space by functional complex formation
Yasushi Tamura1, Miho Iijima, Hiromi Sesaki
1Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
The EMBO Journal
|July 13, 2010
Summary
Mdm35p protein is crucial for importing Ups proteins into the mitochondrial intermembrane space, controlling phospholipid metabolism. This discovery reveals a new mechanism for mitochondrial protein import via functional complexes.
Area of Science:
- Mitochondrial biology
- Protein import mechanisms
- Cellular metabolism
Background:
- Ups1p, Ups2p, and Ups3p are homologous proteins regulating phospholipid metabolism in the mitochondrial intermembrane space (IMS).
- These Ups proteins are atypical IMS proteins, lacking common targeting signals like bipartite presequences and cysteine motifs.
Purpose of the Study:
- To investigate the mechanism of Ups protein import into the mitochondrial IMS.
- To identify proteins involved in the import and function of Ups proteins.
Main Methods:
- In vitro import assays to assess Ups protein import dependency on Mdm35p.
- Analysis of steady-state levels of Ups proteins in mitochondria.
- Phenotypic comparison of Mdm35p-deficient cells with Ups protein-deficient cells.
- Functional assays to evaluate phospholipid metabolism restoration.
Main Results:
- Mdm35p is required for the import of Ups proteins into mitochondria.
- Loss of Mdm35p reduces steady-state levels of Ups proteins and causes phenotypes similar to Ups protein deficiencies.
- Mdm35p forms stable complexes with Ups proteins post-import.
- Restoring Ups protein levels in Mdm35p-deficient mitochondria did not rescue phospholipid metabolism.
Conclusions:
- Mdm35p mediates the import of atypical IMS proteins Ups1p, Ups2p, and Ups3p.
- Functional Ups-Mdm35p complexes are essential for phospholipid metabolism.
- Protein complex formation is a novel mechanism driving mitochondrial protein import.
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