ER targeting of non-imported mitochondrial carrier proteins is dependent on the GET pathway.
ER targeting of non-imported mitochondrial carrier proteins is dependent on the GET pathway.
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DOI：
10.26508/lsa.202000918
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发表时间：
2021-03
影响因子：
4.4
通讯作者：
Hughes AL
中科院分区：
文献类型：
--
作者：
Xiao T;Shakya VP;Hughes AL
GET途径需要将非输入的线粒体载体蛋白靶向内质网，这防止它们沉积到Hsp 42依赖性蛋白灶中。线粒体输入缺陷导致非输入线粒体前体蛋白的毒性积累。已经在芽殖酵母中鉴定了非输入线粒体前体的许多命运，包括蛋白酶体破坏、沉积成蛋白质聚集体以及错误地进入其他细胞器。在细胞器中，ER已成为非进口线粒体蛋白质子集的关键目的地。然而，如何实现ER靶向的各种类型的线粒体蛋白仍然不完全清楚。在这里，我们表明，内源性线粒体跨膜蛋白，特别是那些属于SLC 25 A线粒体载体家族的ER传递依赖于尾锚定蛋白（GET）复合物的引导进入。如果没有功能性GET途径，则注定用于ER的非输入线粒体蛋白质可替代地被隔离到Hsp 42依赖性蛋白质集中区中。GET途径的丧失对经历线粒体输入失败的酵母细胞是有害的，并且阻止线粒体蛋白质经由ER-SURF途径从ER重新输入。总体而言，这项研究概述了GET复合物在ER靶向非进口线粒体载体蛋白中的重要作用。
The GET pathway is required to target non-imported mitochondrial carrier proteins to the endoplasmic reticulum, which prevents their deposition into Hsp42-dependent protein foci. Deficiencies in mitochondrial import cause the toxic accumulation of non-imported mitochondrial precursor proteins. Numerous fates for non-imported mitochondrial precursors have been identified in budding yeast, including proteasomal destruction, deposition into protein aggregates, and mistargeting to other organelles. Amongst organelles, the ER has emerged as a key destination for a subset of non-imported mitochondrial proteins. However, how ER targeting of various types of mitochondrial proteins is achieved remains incompletely understood. Here, we show that the ER delivery of endogenous mitochondrial transmembrane proteins, especially those belonging to the SLC25A mitochondrial carrier family, is dependent on the guided entry of tail-anchored proteins (GET) complex. Without a functional GET pathway, non-imported mitochondrial proteins destined for the ER are alternatively sequestered into Hsp42-dependent protein foci. Loss of the GET pathway is detrimental to yeast cells experiencing mitochondrial import failure and prevents re-import of mitochondrial proteins from the ER via the ER-SURF pathway. Overall, this study outlines an important role for the GET complex in ER targeting of non-imported mitochondrial carrier proteins.
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ER膜蛋白复合物是跨膜结构域插入酶。
DOI：
10.1126/science.aao3099
发表时间：
2018-01-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Guna A;Volkmar N;Christianson JC;Hegde RS
通讯作者：
Hegde RS
影响因子：
4
作者：
Lee, Hsin-Yi;Chao, Jung-Chi;Leu, Jun-Yi
通讯作者：
Leu, Jun-Yi
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.5
作者：
Pagliarini DJ;Calvo SE;Chang B;Sheth SA;Vafai SB;Ong SE;Walford GA;Sugiana C;Boneh A;Chen WK;Hill DE;Vidal M;Evans JG;Thorburn DR;Carr SA;Mootha VK
通讯作者：
Mootha VK
影响因子：
2.6
作者：
Sheff, MA;Thorn, KS
通讯作者：
Thorn, KS