Current Medicinal Chemistry
Current Medicinal Chemistry
3 years ago

Pathophysiological role of mitochondrial potassium channels and their modulation by drugs.

Breschi, Martelli, Citi, Testai, Calderone
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. It is evident that mitochondria are also the targets of multiple drugs; some of these are exactly designed to influence 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. Indeed, they play a decisive role in cardiovascular diseases, particularly in myocardial infarction and neurodegenerative diseases, and they are emerging as promising oncological targets. This review aims 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.

Publisher URL: http://doi.org/10.2174/0929867324666171012115300

DOI: 10.2174/0929867324666171012115300

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