Tail-anchored (TA) membrane proteins have a potential risk to be mistargeted to the mitochondrial outer membrane (OM). Such mislocalized TA proteins can be extracted by the mitochondrial AAA-ATPase Msp1 from the OM and transferred to the ER for ER protein quality control involving ubiquitination by the ER-resident Doa10 complex. Yet it remains unclear how the extracted TA proteins can move to the ER crossing the aqueous cytosol and whether this transfer to the ER is essential for the clearance of mislocalized TA proteins. Here we show by time-lapse microscopy that mislocalized TA proteins, including an authentic ER-TA protein, indeed move from mitochondria to the ER in a manner strictly dependent on Msp1 expression. The Msp1-dependent mitochondria-to-ER transfer of TA proteins is blocked by defects in the GET system, and this block is not due to impaired Doa10 functions. Thus, the GET pathway facilitates the transfer of mislocalized TA proteins from mitochondria to the ER.

中文翻译：

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GET 途径介导错误定位的尾部锚定蛋白从线粒体转移到 ER

尾锚定 (TA) 膜蛋白存在误定位至线粒体外膜 (OM) 的潜在风险。这种错误定位的 TA 蛋白可以通过线粒体 AAA-ATPase Msp1 从 OM 中提取，并转移到 ER 进行 ER 蛋白质量控制，涉及 ER 驻留 Doa10 复合物的泛素化。然而，目前尚不清楚提取的 TA 蛋白如何穿过水性细胞质转移到 ER，以及这种转移到 ER 是否对于清除错误定位的 TA 蛋白至关重要。在这里，我们通过延时显微镜显示，错误定位的 TA 蛋白（包括真正的 ER-TA 蛋白）确实以严格依赖于 Msp1 表达的方式从线粒体移动到 ER。TA 蛋白依赖于 Msp1 的线粒体向 ER 的转移被 GET 系统的缺陷所阻断，并且这种阻断并不是由于 Doa10 功能受损所致。因此，GET 途径促进错误定位的 TA 蛋白从线粒体转移到 ER。