Title:Pathophysiological Role of Mitochondrial Potassium Channels and their Modulation by Drugs
Volume: 25
Issue: 23
Author(s): Valentina Citi, Vincenzo Calderone, Alma Martelli, Maria C. Breschi and Lara Testai*
Affiliation:
- Department of Pharmacy, via Bonanno 6 - 56126, Pisa,Italy
Keywords:
Mitochondrial potassium channels, cardiovascular diseases, neurological diseases, oncological diseases,
phosphorylation, ROS.
Abstract: 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.
