OPTN binds ATG9A

During PINK1:PRKN-mediated mitophagy, the autophagy receptor optineurin (OPTN) forms a complex with the autophagy-related 9A (ATG9A) protein, a membrane-spanning protein that is recruited to the autophagosomal formation site (Yamamoto H et al., 2012; Yamano K et al., 2020). ATG9A localizes to the cytoplasmic single-membrane vesicles, termed ATG9 vesicles (Yamamoto H et al., 2012). OPTN recruits cytoplasmic ATG9A vesicles to damaged mitochondria (Yamano K et al., 2020), where these vesicles provide membrane contact sites delivering proteins and lipids during autophagosome formation (Yamamoto H et al., 2012; reviewed by Nishimura T & Tooze SA 2020). The leucine zipper domain of OPTN is required for the interaction with ATG9A (Yamano K et al., 2020). Disruptions of OPTN:ATG9A interaction inhibits mitophagy (Yamano K et al., 2020). Interactions between OPTN and other ATG proteins such as microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B or LC3) are implicated in autophagy.

在PINK1:PRKN介导的线粒体自噬过程中，自噬受体optineurin（OPTN）与自噬相关蛋白9A（ATG9A）形成复合物，ATG9A是一种跨膜蛋白，被招募至自噬体形成位点（Yamamoto H 等，2012；Yamano K 等，2020）。ATG9A定位于细胞质单层膜囊泡，被称为ATG9囊泡（Yamamoto H 等，2012）。OPTN将细胞质中的ATG9A囊泡招募至受损的线粒体（Yamano K 等，2020），在这些囊泡中，提供了膜接触位点，从而在自噬体形成过程中传递蛋白质和脂质（Yamamoto H 等，2012；Nishimura T & Tooze SA 2020年综述）。OPTN的亮氨酸拉链结构域对于与ATG9A的相互作用是必需的（Yamano K 等，2020）。OPTN与ATG9A的相互作用中断将抑制线粒体自噬（Yamano K 等，2020）。OPTN与其他ATG蛋白，如微管相关蛋白1A/1B轻链3B（MAP1LC3B或LC3）之间的相互作用与自噬有关。