Mitochondrial K+ channels and their implications for disease mechanisms

The field of mitochondrial ion channels underwent a rapid development during the last decade, thanks to the molecular identification of some of the nuclear-encoded organelle channels and to advances in strategies allowing specific pharmacological targeting of these proteins. Thereby, genetic tools and specific drugs aided definition of the relevance of several mitochondrial channels both in physiological as well as pathological conditions. Unfortunately, in the case of mitochondrial K+ channels, efforts of genetic manipulation provided only limited results, due to their dual localization to mitochondria and to plasma membrane in most cases. Although the impact of mitochondrial K+ channels on human diseases is still far from being genuinely understood, pre-clinical data strongly argue for their substantial role in the context of several pathologies, including cardiovascular and neurodegenerative diseases as well as cancer. Importantly, these channels are druggable targets, and their in-depth investigation could thus pave the way to the development of innovative small molecules with huge therapeutic potential. In the present review we summarize the available experimental evidence that mechanistically link mitochondrial potassium channels to the above pathologies and underline the possibility of exploiting them for therapy. (C) 2021 Published by Elsevier Inc.

Automated summary

The field of mitochondrial ion channels has rapidly developed in the past decade due to molecular identification and specific pharmacological targeting. Despite challenges in genetic manipulation of mitochondrial K+ channels, they are recognized to play important roles in various pathologies and are druggable targets for potential therapeutic interventions. The in-depth investigation of mitochondrial potassium channels may lead to the development of innovative small molecules with significant therapeutic potential.