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

• Verfasst von: Krumpe, Katrin [VerfasserIn]
• Verfasst von: Özbalcı, Çağakan [VerfasserIn]
• Verfasst von: Brügger, Britta [VerfasserIn]
• Titel: Ergosterol content specifies targeting of tail-anchored proteins to mitochondrial outer membranes
• Verf.angabe: Katrin Krumpe, Idan Frumkin, Yonatan Herzig, Nitzan Rimon, Cagakan Özbalci, Britta Brügger, Doron Rapaport, and Maya Schuldiner
• Umfang: 9 S.
• Fussnoten: Gesehen am 31.08.2018
• Titel Quelle: Enthalten in: Molecular biology of the cell
• Jahr Quelle: 2012
• Band/Heft Quelle: 23(2012), 20, S. 3927-3935
• ISSN Quelle: 1939-4586
• DOI: doi:10.1091/mbc.E11-12-0994
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 158058750X

Abstract

Mitochondrial outer membrane tail-anchored proteins are a unique class of membrane proteins with unknown targeting mechanism. Using two high-throughput microscopy screens, we demonstrate that the inherent differences in membrane composition between organelle membranes is enough to determine membrane integration specificity in a living cell., 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.