Pathophysiological role of mitochondrial potassium channels and their modulation by drugs

Background: Mitochondria play a central role in ATP-generating processes. Indeed, in mammalian tissues, up to 90% of ATP is generated by mitochondria through the process of oxidative phosphorylation; furthermore, mitochondria are involved in multiple signal transduction pathways. A rapidly expanding body of literature has confirmed that mitochondria play a pivotal role in apoptosis, cardio-and neuro-protection, and various neurodegenerative disorders, ranging from Parkinson’s to Alzheimer’s disease. Mitochondria are also the targets of multiple drugs, some of these are specifically designed to affect mitochondrial function, while others have primary targets in other cellular locations but may interact with mitochondria because of the presence of numerous targets on this organelle. In this regard, mitochondrial potassium (mitoK) channels play a critical role in mitochondrial function and, consequently, in the metabolism of the whole cell. Objective: To describe mitoK channels from a structural point of view and investigate their pathophysiological roles, focusing on possible specific modulators that might be useful as pharmacological tools in the treatment of various pathologies characterized by mitoK involvement. Results: mitoK channels play a decisive role in several pathologies, including cardiovascular diseases, particularly in myocardial infarction and neurodegenerative diseases, and they are emerging as promising oncological targets. Conclusions: mitoK channels represent novel targets, and mitoK channel modulators represent an exciting tool for pharmacological intervention against such pathological conditions.