Defects in autophagy cause problems in metabolism, development, and disease. The autophagic clearance of mitochondria, mitophagy, is impaired by the loss of Vps13D. Here, we discover that Vps13D regulates mitophagy in a pathway that depends on the core autophagy machinery by regulating Atg8a and ubiquitin localization. This process is Pink1 dependent, with loss of pink1 having similar autophagy and mitochondrial defects as loss of vps13d. The role of Pink1 has largely been studied in tandem with Park/Parkin, an E3 ubiquitin ligase that is widely considered to be crucial in Pink1-dependent mitophagy. Surprisingly, we find that loss of park does not exhibit the same autophagy and mitochondrial deficiencies as vps13d and pink1 mutant cells and contributes to mitochondrial clearance through a pathway that is parallel to vps13d. These findings provide a Park-independent pathway for Pink1-regulated mitophagy and help to explain how Vps13D regulates autophagy and mitochondrial morphology and contributes to neurodegenerative diseases.

中文翻译：

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Vps13D 在 Pink1 依赖性和 Parkin 独立的线粒体自噬途径中发挥作用

自噬缺陷会导致新陈代谢、发育和疾病的问题。Vps13D 的缺失会损害线粒体的自噬清除（线粒体自噬）。在这里，我们发现 Vps13D 通过调节 Atg8a 和泛素定位来调节线粒体自噬，该途径依赖于核心自噬机制。这个过程依赖于 Pink1，pink1 的缺失与 vps13d 的缺失具有相似的自噬和线粒体缺陷。Pink1 的作用在很大程度上与 Park/Parkin 一起进行了研究，Park/Parkin 是一种 E3 泛素连接酶，被广泛认为在 Pink1 依赖性线粒体自噬中至关重要。令人惊讶的是，我们发现park的丢失并不表现出与vps13d和pink1突变细胞相同的自噬和线粒体缺陷，并且通过与vps13d平行的途径有助于线粒体清除。这些发现为 Pink1 调节的线粒体自噬提供了一条独立于 Park 的途径，并有助于解释 Vps13D 如何调节自噬和线粒体形态并导致神经退行性疾病。