Lysosome pH‐regulated H+/K+ switching channel involved in maintaining lysosomal homeostasis

Abstract

Lysosomal pH setpoint and H+ homeostasis is key to the lysosome's functions. The Parkinson's disease‐risk protein TMEM175, originally identified as lysosomal K+ channel, works as a H+‐activated H+ channel and discharges the lysosomal H+ store when it is hyper‐acidified. Yang et al. indicate that TMEM175 is permeable for both K+ and H+ in the same pore and charges the lysosome with H+ under certain conditions. The charge and discharge functions are under regulation of the lysosomal matrix and glycocalyx layer. Their presented work indicates that TMEM175 performs as a multi‐functional channel regulating lysosomal pH in response to physiological conditions.