Mitochondrial Ion Channels

Abstract

Mitochondria are involved in multiple cellular tasks, such as ATP synthesis, metabolism, metabolite and ion transport, regulation of apoptosis, inflammation, signaling, and inheritance of mitochondrial DNA. The majority of the correct functioning of mitochondria is based on the large electrochemical proton gradient, whose component, the inner mitochondrial membrane potential, is strictly controlled by ion transport through mitochondrial membranes. Consequently, mitochondrial function is critically dependent on ion homeostasis, the disturbance of which leads to abnormal cell functions. Therefore, the discovery of mitochondrial ion channels influencing ion permeability through the membrane has defined a new dimension of the function of ion channels in different cell types, mainly linked to the important tasks that mitochondrial ion channels perform in cell life and death. This review summarizes studies on animal mitochondrial ion channels with special focus on their biophysical properties, molecular identity, and regulation. Additionally, the potential of mitochondrial ion channels as therapeutic targets for several diseases is briefly discussed.

Solute Transport through Mitochondrial Porins In Vitro and In Vivo

“…It is noteworthy that this simple method was successfully used for the purification of different eukaryotic porins by the Bari/Catania group in their research into mitochondria [ 34 , 35 , 36 , 37 , 38 ]. Using this method many mitochondrial porins could be studied in reconstituted systems [ 33 , 39 , 40 ]. Similarly, the structure and function of eukaryotic porins and their interaction with different detergents could also be studied using the simple purification procedure by passing total mitochondrial membrane proteins dissolved in detergent through an HTP/celite column [ 41 , 42 , 43 , 44 ].…”

“…More than one hundred sequences of eukaryotic porins are known to date. Although the sequence identity between them is relatively low, the polypeptide length and, in particular, the electrophysiological characteristics are highly preserved [ 33 , 39 , 40 , 56 , 64 ]. This means that all eukaryotic porins studied to date are anion-selective in the open state [ 8 , 9 , 16 , 39 , 40 ].…”

“…Although the sequence identity between them is relatively low, the polypeptide length and, in particular, the electrophysiological characteristics are highly preserved [ 33 , 39 , 40 , 56 , 64 ]. This means that all eukaryotic porins studied to date are anion-selective in the open state [ 8 , 9 , 16 , 39 , 40 ]. Similarly, eukaryotic porins form voltage-dependent channels that switch to lower conductance cation selective states at voltages beginning with about 20 mV.…”

The BKCa (slo) channel regulates the cardiac function of Drosophila

“…In the heart, the expression of BK Ca is vital for cardiac rhythm by regulating the function of SA node cells (Imlach et al., 2010 ; Lai et al., 2014 ). In mammalian adult cardiomyocytes, BK Ca channels are exclusively present in the inner mitochondrial membrane (Singh et al., 2013 ; Szabo & Szewczyk, 2023 ). In the inner membrane of mitochondria, activation of the BK Ca channel results in cardioprotection from ischemia–reperfusion (IR) injury (Singh et al., 2013 ; Szteyn & Singh, 2020 ).…”

mitoBKCais functionally expressed in murine and human breast cancer cells and promotes metabolic reprogramming

“…Accordingly, in BC cells (BCCs), an upregulation of BKCa has been associated with increased malignancy (Huang and Jan, 2014;Mohr et al, 2022;Oeggerli et al, 2012). However, besides their localization in the PM, several K + channels, including BKCa, have also been identified in the inner mitochondrial membrane (IMM) (mitoBKCa), a topic which has been extensively reviewed recently (Checchetto et al, 2021;Kulawiak and Szewczyk, 2022;Szabo and Szewczyk, 2023;Szewczyk et al, 2009;Wrzosek et al, 2020). mitoBKCa was first described by Siemen et al in a human glioma cell line more than 20 years ago (Siemen et al, 1999).…”