LRRC8 family proteins within lysosomes regulate cellular osmoregulation and enhance cell survival to multiple physiological stresses

• DOI: 10.1073/pnas.2016539117
• Publication Date: 2020-11-03T01:31:03Z
• Authors: Ping Li; Meiqin Hu; Ce Wang; Xinghua Feng; ZhuangZhuang Zhao; Ying Yang; Nirakar Sahoo; Mingxue Gu; Yexin Yang; Shiyu Xiao; Rajan Sah; Timothy L. Cover; Janet Chou; Raif Geha; Fernando Benavides; Richard I. Hume; Haoxing Xu
• Keywords: Organelle; Homeostasis

Significance Cells encountering physiological stresses often become vacuolated, but the source of vacuoles and their role in causing or ameliorating necrotic cell death are unclear. Studies cells responding to hypoosmotic, hypoxic, hypothermic stress revealed that 1) derived from lysosomes, 2) many subsequently undergo exocytosis, 3) blocking either vacuolation vacuole exocytosis by genetic pharmacological approaches led greatly increased death. By storing then expelling excess water, lysosome-derived maintain cytosolic water homeostasis relieve membrane stress. This basic cellular function was present all mammalian types tested required ionic strength-sensitive ion channels formed LRRC8 proteins on lysosomal membranes (Lyso-VRACs) acting parallel with plasma VRAC channels.