Annexins A1 and A2 are recruited to larger lysosomal injuries independently of ESCRTs to promote repair

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.