Mitochondrial Ion Channels of the Inner Membrane and Their Regulation in Cell Death Signaling

Mitochondria are bioenergetic organelles with a plethora of fundamental functions ranging from metabolism and ATP production to modulation of signaling events leading to cell survival or cell death. Ion channels located in the outer and inner mitochondrial membranes critically control mitochondrial function and, as a consequence, also cell fate. Opening or closure of mitochondrial ion channels allow the fine-tuning of mitochondrial membrane potential, ROS production, and function of the respiratory chain complexes. In this review, we critically discuss the intracellular regulatory factors that affect channel activity in the inner membrane of mitochondria and, indirectly, contribute to cell death. These factors include various ligands, kinases, second messengers, and lipids. Comprehension of mitochondrial ion channels regulation in cell death pathways might reveal new therapeutic targets in mitochondria-linked pathologies like cancer, ischemia, reperfusion injury, and neurological disorders.

Automated summary

Mitochondria are vital organelles involved in cell survival and death. Ion channels in the inner membrane of mitochondria play a crucial role in regulating mitochondrial function and ultimately affecting cell fate. Understanding the regulation of mitochondrial ion channels may lead to the identification of new therapeutic targets for mitochondria-related pathologies.