Uth1 is a mitochondrial inner membrane protein dispensable for post‐log‐phase and rapamycin‐induced mitophagy
Uth1 is a mitochondrial inner membrane protein dispensable for post‐log‐phase and rapamycin‐induced mitophagy
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DOI：
10.1111/febs.12468
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发表时间：
2013-10
期刊：
影响因子：
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通讯作者：
Evelyn Welter;M. Montino;R. Reinhold;P. Schlotterhose;R. Krick;Jan Dudek;P. Rehling;M. Thumm
中科院分区：
文献类型：
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作者：
Evelyn Welter;M. Montino;R. Reinhold;P. Schlotterhose;R. Krick;Jan Dudek;P. Rehling;M. Thumm
线粒体通过自噬过程被翻转，称为线粒体自噬。这一过程被认为是去除受损、多余和老化的细胞器。然而，很少有人知道有缺陷的细胞器是如何识别的，什么类型的损伤诱导营业额，以及是否有一组相同的因素有助于在不同的条件下降解。在这里，我们系统地比较了对数期后和雷帕霉素诱导的线粒体自噬的速率和对线粒体自噬特异性蛋白的需求。为了具体评估受损线粒体的线粒体自噬，我们分析了由于缺乏线粒体AAA-蛋白酶Yme 1而积累易于降解的蛋白质的细胞。虽然在所有测试条件下都需要自噬32（Atg 32），但Atg 33的功能在对数期后和雷帕霉素诱导的线粒体自噬中可以部分绕过。出乎意料的是，我们发现Uth 1与线粒体自噬有关。对其线粒体定位的重新评估显示，Uth 1是线粒体内膜的一种蛋白质，由可切割的N末端前序列靶向。与我们的功能分析一致，这一发现排除了Uth 1作为线粒体表面受体的作用。
Mitochondria are turned over by an autophagic process termed mitophagy. This process is considered to remove damaged, superfluous and aged organelles. However, little is known about how defective organelles are recognized, what types of damage induce turnover, and whether an identical set of factors contributes to degradation under different conditions. Here we systematically compared the mitophagy rate and requirement for mitophagy‐specific proteins during post‐log‐phase and rapamycin‐induced mitophagy. To specifically assess mitophagy of damaged mitochondria, we analyzed cells accumulating proteins prone to degradation due to lack of the mitochondrial AAA‐protease Yme1. While autophagy 32 (Atg32) was required under all tested conditions, the function of Atg33 could be partially bypassed in post‐log‐phase and rapamycin‐induced mitophagy. Unexpectedly, we found that Uth1 was dispensable for mitophagy. A re‐evaluation of its mitochondrial localization revealed that Uth1 is a protein of the inner mitochondrial membrane that is targeted by a cleavable N‐terminal pre‐sequence. In agreement with our functional analyses, this finding excludes a role of Uth1 as a mitochondrial surface receptor.