Ca²⁺-sensor ALG-2 engages ESCRTs to enhance lysosomal membrane resilience to osmotic stress.

ABSTRACT: Lysosomes are central players in cellular catabolism, signaling, and metabolic regulation. Cellular and environmental stresses that damage lysosomal membranes can compromise their function and release toxic content into the cytoplasm. Here, we examine how cells respond to osmotic stress within lysosomes. Using sensitive assays of lysosomal leakage and rupture, we examine acute effects of the osmotic disruptant glycyl-L-phenylalanine 2-naphthylamide (GPN). Our findings reveal that low concentrations of GPN rupture a small fraction of lysosomes, but surprisingly trigger Ca²⁺ release from nearly all. Chelating cytoplasmic Ca²⁺ makes lysosomes more sensitive to GPN-induced rupture, suggesting a role for Ca²⁺ in lysosomal membrane resilience. GPN-elicited Ca

SUBMITTER: Chen W 

PROVIDER: S-EPMC11145288 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature