Tonic inhibition of the chloride/proton antiporter ClC-7 by PI(3,5)P2 is crucial for lysosomal pH maintenance.

ABSTRACT: The acidic luminal pH of lysosomes, maintained within a narrow range, is essential for proper degrative function of the organelle and is generated by the action of a V-type H⁺ ATPase, but other pathways for ion movement are required to dissipate the voltage generated by this process. ClC-7, a Cl^-/H⁺ antiporter responsible for lysosomal Cl^- permeability, is a candidate to contribute to the acidification process as part of this 'counterion pathway' The signaling lipid PI(3,5)P2 modulates lysosomal dynamics, including by regulating lysosomal ion channels, raising the possibility that it could contribute to lysosomal pH regulation. Here, we demonstrate that depleting PI(3,5)P2 by inhibiting the kinase PIKfyve causes lysosomal hyperacidification, prim

SUBMITTER: Leray X 

PROVIDER: S-EPMC9242644 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature