Metabolic energy sensing by mammalian CLC anion/proton exchangers.

ABSTRACT: CLC anion/proton exchangers control the pH and [Cl^- ] of the endolysosomal system that is essential for cellular nutrient uptake. Here, we use heterologous expression and whole-cell electrophysiology to investigate the regulation of the CLC isoforms ClC-3, ClC-4, and ClC-5 by the adenylic system components ATP, ADP, and AMP. Our results show that cytosolic ATP and ADP but not AMP and Mg²⁺ -free ADP enhance CLC ion transport. Biophysical analysis reveals that adenine nucleotides alter the ratio between CLC ion transport and CLC gating charge and shift the CLC voltage-dependent activation. The latter effect is suppressed by blocking the intracellular entrance of the proton transport pathway. We suggest, therefore, that adenine nucleotides regulate the internal proton de

SUBMITTER: Grieschat M 

PROVIDER: S-EPMC7271328 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature