DETERMINANTS, MAINTENANCE, AND FUNCTION OF ORGANELLAR pH

The protonation state of soluble and membrane-associated macromolecules dictates their charge, conformation, and functional activity. In addition, protons (H+ or their equivalents) partake in numerous metabolic reactions and serve as a source of electrochemical energy to drive the transmembrane transport of both organic and inorganic substrates. Stringent regulation of the intracellular pH is therefore paramount to homeostasis. Although the regulation of the cytosolic pH has been studied extensively, our understanding of the determinants of the H+ concentration ([H+]) of intracellular organelles has developed more slowly, limited by their small size and inaccessibility. Recently, however, targeting of molecular probes to the organellar lumen together with advances in genomic, proteomic, and electrophysiological techniques have led to the identification and characterization of unique pumps, channels, and transporters responsible for the establishment and maintenance of intraorganellar pH. These developments and their implications for cellular function in health and disease are the subject of this review.

Automated summary

The protonation state of macromolecules affects their properties and functions. Protons are also involved in metabolic reactions and drive the transmembrane transport of substances. Maintaining the intracellular pH is crucial for cellular stability. Recent advancements in molecular probes and genomic, proteomic, and electrophysiological techniques have enhanced our understanding of the regulation of intracellular pH and its implications for cellular function in health and disease.