Liu Xu, Wen Xin, Klionsky Daniel J
Life Sciences Institute, and the Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Contact (Thousand Oaks). 2018 Jan-Dec;2. doi: 10.1177/2515256418821584. Epub 2019 Jan 8.
Peroxisomes play important roles in lipid metabolism. Surplus or damaged peroxisomes can be selectively targeted for autophagic degradation, a process termed pexophagy. Maintaining a proper level of pexophagy is critical for cellular homeostasis. Here we found that endoplasmic reticulum (ER)-mitochondria contact sites are necessary for efficient pexophagy. During pexophagy, the peroxisomes destined for degradation are adjacent to the ER-mitochondria encounter structure (ERMES) that mediates formation of ER- mitochondria contacts; disruption of the ERMES results in a severe defect in pexophagy. We show that a mutant form of Mdm34, a component of the ERMES, which impairs ERMES formation and diminishes its association with the peroxisomal membrane protein Pex11, also leads to defects in pexophagy. The dynamin-related GTPase Vps1, which is specific for peroxisomal fission, is recruited to the peroxisomes at ER-mitochondria contacts by the selective autophagy scaffold Atg11 and the pexophagy receptor Atg36, facilitating peroxisome degradation.
过氧化物酶体在脂质代谢中发挥重要作用。多余或受损的过氧化物酶体可被选择性地靶向进行自噬降解，这一过程称为过氧化物酶体自噬。维持适当水平的过氧化物酶体自噬对于细胞稳态至关重要。在这里，我们发现内质网（ER）-线粒体接触位点对于高效的过氧化物酶体自噬是必需的。在过氧化物酶体自噬过程中，注定要被降解的过氧化物酶体与介导内质网-线粒体接触形成的内质网-线粒体相遇结构（ERMES）相邻；ERMES的破坏会导致过氧化物酶体自噬严重缺陷。我们表明，ERMES的一个组分Mdm34的突变形式会损害ERMES的形成并减少其与过氧化物酶体膜蛋白Pex11的结合，这也会导致过氧化物酶体自噬缺陷。动力蛋白相关的GTP酶Vps1，它对过氧化物酶体分裂具有特异性，通过选择性自噬支架Atg11和过氧化物酶体自噬受体Atg36被募集到内质网-线粒体接触处的过氧化物酶体上，促进过氧化物酶体降解。
