Mitochondrial potassium channels: mitochondria-specific mechanism of regulation

Abstract Potassium channels identified in the plasma membrane play a crucial role, particularly in generating action potentials in excitable cells. Recently, potassium channels have also been discovered in intracellular organelles, including the inner mitochondrial membrane (IMM), which share many properties with their plasma membrane counterparts. Mitochondrial potassium channels exhibit similar biophysical, pharmacological, and regulatory characteristics, reflecting their common molecular origin. However, differences in potassium channel activity may result from differences in isoforms as well as from the specific ionic, protein, and lipid environments associated with their distinct subcellular locations. In particular, the IMM imposes unique conditions that shape the regulation of mitochondrial potassium channels. These include close proximity to the respiratory chain, high mitochondrial metabolic activity, a pronounced transmembrane potential, and pH gradients. This review examines how these mitochondrial-specific factors influence the function of mitochondrial potassium channels. A deeper understanding of how the IMM environment modulates mitochondrial channel activity will not only expand our knowledge of mitochondrial physiology but may also pave the way for new therapeutic strategies targeting mitochondrial dysfunction and the role of mitochondrial potassium channels in human diseases.