Yim Willa Wen-You, Yamamoto Hayashi, Mizushima Noboru
Department of Biochemistry and Molecular Biology, Graduate School of Medicine, The University of Tokyo, Japan.
FEBS Lett. 2022 Apr;596(8):991-1003. doi: 10.1002/1873-3468.14329. Epub 2022 Mar 21.
Damaged lysosomes can be repaired by calcium release-dependent recruitment of the ESCRT machinery. However, the involvement of annexins, another group of calcium-responding membrane repair proteins, has not been fully addressed. Here, we show that although all ubiquitously expressed annexins (ANXA1, A2, A4, A5, A6, A7, and A11) localize to damaged lysosomes, only ANXA1 and ANXA2 are important for repair. Their recruitment is calcium-dependent, ESCRT-independent, and selective towards lysosomes with large injuries. Lysosomal leakage was more severe when ANXA1 or ANXA2 was depleted compared to that of ESCRT components. These findings suggest that ANXA1 and ANXA2 constitute an additional repair mechanism that serves to minimize leakage from damaged lysosomes.
受损的溶酶体可通过钙释放依赖的转运所需内体分选复合体（ESCRT）机制招募进行修复。然而，膜联蛋白（另一类钙响应性膜修复蛋白）的作用尚未得到充分研究。在这里，我们表明，尽管所有普遍表达的膜联蛋白（膜联蛋白A1、A2、A4、A5、A6、A7和A11）都定位于受损的溶酶体，但只有膜联蛋白A1和A2对修复很重要。它们的招募是钙依赖性的、不依赖于ESCRT的，并且对损伤较大的溶酶体具有选择性。与ESCRT组分缺失相比，膜联蛋白A1或A2缺失时溶酶体泄漏更严重。这些发现表明，膜联蛋白A1和A2构成了一种额外的修复机制，可将受损溶酶体的泄漏降至最低。
