Ergosterol content specifies targeting of tail-anchored proteins to mitochondrial outer membranes

Tail-anchored (TA) proteins have a single C-terminal transmembrane domain, making their biogenesis dependent on posttranslational translocation. Despite their importance, no dedicated insertion machinery has been uncovered for mitochondrial outer membrane (MOM) TA proteins. To decipher the molecular...

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Bibliographic Details
Published in:Molecular biology of the cell 2012-10, Vol.23 (20), p.3927-3935
Main Authors: Krumpe, Katrin, Frumkin, Idan, Herzig, Yonatan, Rimon, Nitzan, Özbalci, Cagakan, Brügger, Britta, Rapaport, Doron, Schuldiner, Maya
Format: Article
Language:English
Subjects:
Endoplasmic Reticulum - metabolism
Ergosterol - metabolism
Gene Deletion
Green Fluorescent Proteins - metabolism
Mitochondria - metabolism
Mitochondrial Membranes - metabolism
Mutation - genetics
Protein Structure, Tertiary
Protein Transport
Saccharomyces cerevisiae - cytology
Saccharomyces cerevisiae - metabolism
Saccharomyces cerevisiae Proteins - chemistry
Saccharomyces cerevisiae Proteins - metabolism
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Summary:Tail-anchored (TA) proteins have a single C-terminal transmembrane domain, making their biogenesis dependent on posttranslational translocation. Despite their importance, no dedicated insertion machinery has been uncovered for mitochondrial outer membrane (MOM) TA proteins. To decipher the molecular mechanisms guiding MOM TA protein insertion, we performed two independent systematic microscopic screens in which we visualized the localization of model MOM TA proteins on the background of mutants in all yeast genes. We could find no mutant in which insertion was completely blocked. However, both screens demonstrated that MOM TA proteins were partially localized to the endoplasmic reticulum (ER) in spf1 cells. Spf1, an ER ATPase with unknown function, is the first protein shown to affect MOM TA protein insertion. We found that ER membranes in spf1 cells become similar in their ergosterol content to mitochondrial membranes. Indeed, when we visualized MOM TA protein distribution in yeast strains with reduced ergosterol content, they phenocopied the loss of Spf1. We therefore suggest that the inherent differences in membrane composition between organelle membranes are sufficient to determine membrane integration specificity in a eukaryotic cell.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.e11-12-0994