Proton-selective conductance and gating of the lysosomal cation channel TMEM175.

ABSTRACT: The lysosomal cation channel TMEM175 plays a key role in luminal pH homeostasis and lysosome function, with aberrant activity linked to Parkinson's disease. Although initially described as a K⁺-selective channel, TMEM175 exhibits substantial H⁺ permeability. Here, we dissect complex changes affecting human TMEM175 conductance and ionic properties of TMEM175-mediated current in response to pH shifts on the luminal side of the protein. A drop in pH from 7.4 to 4.7 on the side equivalent to the lysosomal lumen triggers a sustained increase in TMEM175-mediated inward and outward currents, which is accompanied by a transient shift in the reversal potential (E_rev) toward the theoretical equilibrium voltage for H⁺, yet remaining ~100 mV below the expect

SUBMITTER: Schulze T 

PROVIDER: S-EPMC12818570 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature