Sterol Oxidation Mediates Stress-Responsive Vms1 Translocation to Mitochondria

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2017 Nov 18

PMID 29149595

Citations 19

Authors

Jason R Nielson

Eric K Fredrickson

T Cameron Waller

Olga Zurita Rendon

Heidi L Schubert

Zhenjian Lin

Christopher P Hill

Jared Rutter

Affiliations

Soon will be listed here.

Abstract

Vms1 translocates to damaged mitochondria in response to stress, whereupon its binding partner, Cdc48, contributes to mitochondrial protein homeostasis. Mitochondrial targeting of Vms1 is mediated by its conserved mitochondrial targeting domain (MTD), which, in unstressed conditions, is inhibited by intramolecular binding to the Vms1 leucine-rich sequence (LRS). Here, we report a 2.7 Å crystal structure of Vms1 that reveals that the LRS lies in a hydrophobic groove in the autoinhibited MTD. We also demonstrate that the oxidized sterol, ergosterol peroxide, is necessary and sufficient for Vms1 localization to mitochondria, through binding the MTD in an interaction that is competitive with binding to the LRS. These data support a model in which stressed mitochondria generate an oxidized sterol receptor that recruits Vms1 to support mitochondrial protein homeostasis.

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