Development of a chemogenetic approach to manipulate intracellular pH

Chemogenetic Operation of iNTRacellular prOton Levels (pH-Control) is a novel substrate-based enzymatic method that enables precise spatio-temporal control of ultra-local acidification in cultured cell lines and primary neurons. The genetically encoded biosensor SypHer3s showed that pH-Control effectively acidifies cytosolic, mitochondrial, and nuclear pH exclusively in the presence of beta-Chloro-D-alanine in living cells in a concentra-tion-dependent manner. The pH-Control approach is promising for investigating the ultra-local pH imbalance associated with many diseases.