Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan, China.
Luoyang Normal University, Henan, China.
Cell Death Differ. 2021 Mar;28(3):1076-1090. doi: 10.1038/s41418-020-00638-2. Epub 2020 Oct 21.
Selective autophagic degradation of mitochondria (mitophagy) is important in maintaining proper cellular homeostasis. Here, we found that SPATA33 is a novel autophagy mediator for mitophagy in testis. The SPATA33 protein localizes on mitochondria via its binding of the carboxyl terminal with the outer mitochondrial membrane protein VDAC2. Upon starvation induction, SPATA33 is recruited to autophagosome by binding the autophagy machinery ATG16L1 via its N-terminal along with mitochondria. Notably, Spata33 knockout inhibited autophagy and overexpression can promote autophagosome formation for mitochondrial sequestration. Therefore, SPATA33 confers selectivity for mitochondrial degradation and promotes mitophagy in male germline cells.
选择性自噬性降解线粒体(mitophagy)对于维持细胞内环境稳态非常重要。在这里,我们发现 SPATA33 是睾丸中参与线粒体自噬的一种新的自噬调节蛋白。SPATA33 蛋白通过其羧基末端与外膜蛋白 VDAC2 的结合定位于线粒体上。在饥饿诱导时,SPATA33 通过其 N 末端与 ATG16L1 结合,同时与线粒体一起被招募到自噬体。值得注意的是,Spata33 敲除抑制了自噬,而过表达可以促进自噬体形成以隔离线粒体。因此,SPATA33 赋予了线粒体降解的选择性,并促进了雄性生殖细胞中的线粒体自噬。