Laboratory of Mitochondrial Dynamics, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.
Laboratory of Mitochondrial Dynamics, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.
Biochem Biophys Res Commun. 2018 Sep 3;503(1):14-20. doi: 10.1016/j.bbrc.2018.04.114. Epub 2018 May 10.
Mitophagy is an evolutionarily conserved autophagy pathway that selectively eliminates mitochondria to control mitochondrial quality and quantity. Although mitophagy is thought to be crucial for cellular homeostasis, how this catabolic process is regulated remains largely unknown. Here we demonstrate that mitophagy during prolonged respiratory growth is strongly impaired in yeast cells lacking Get1/2, a transmembrane complex mediating insertion of tail-anchored (TA) proteins into the endoplasmic reticulum (ER) membrane. Under the same conditions, loss of Get1/2 caused only slight defects in other types of selective and bulk autophagy. In addition, mitophagy and other autophagy-related processes are mostly normal in cells lacking Get3, a cytosolic ATP-driven chaperone that promotes delivery of TA proteins to the Get1/2 complex. We also found that Get1/2-deficient cells exhibited wildtype-like induction and mitochondrial localization of Atg32, a protein essential for mitophagy. Notably, Get1/2 is important for Atg32-independent, ectopically promoted mitophagy. Together, we propose that Get1/2-dependent TA protein(s) and/or the Get1/2 complex itself may act specifically in mitophagy.
自噬是一种进化上保守的自噬途径，它选择性地消除线粒体以控制线粒体的质量和数量。虽然自噬被认为对细胞内稳态至关重要，但这个分解过程是如何被调节的仍然很大程度上未知。在这里，我们证明在酵母细胞中，缺乏 Get1/2（一种介导将尾部锚定（TA）蛋白插入内质网膜的跨膜复合物）会强烈损害在长时间呼吸生长期间的线粒体自噬。在相同的条件下，Get1/2 的缺失仅导致其他类型的选择性和批量自噬出现轻微缺陷。此外，在缺乏 Get3（一种促进 TA 蛋白向 Get1/2 复合物传递的细胞质 ATP 驱动的伴侣蛋白）的细胞中，线粒体自噬和其他与自噬相关的过程大多正常。我们还发现，Get1/2 缺陷型细胞表现出与野生型相似的 Atg32 的诱导和线粒体定位，Atg32 是线粒体自噬所必需的一种蛋白。值得注意的是，Get1/2 对于非依赖性、异位促进的线粒体自噬是重要的。总之，我们提出 Get1/2 依赖性 TA 蛋白（和/或）Get1/2 复合物本身可能特异性地作用于线粒体自噬。
