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.

中文翻译：

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甾醇氧化介导应力响应Vms1易位至线粒体。

Vms1响应压力转位至受损的线粒体，随后其结合伴侣Cdc48促进了线粒体蛋白质的体内稳态。Vms1的线粒体靶向作用是由其保守的线粒体靶向结构域（MTD）介导的，在不受压力的情况下，分子内与富含Vms1亮氨酸的序列（LRS）结合会抑制线粒体靶向结构域。在这里，我们报告了Vms1的2.7晶体结构，该结构揭示LRS位于自抑制MTD的疏水槽中。我们还证明了氧化的固醇，麦角固醇过氧化物，对于Vms1定位到线粒体是必要的和充分的，这是通过在与LRS的结合竞争的相互作用中结合MTD来实现的。