AUTHOR=Urbani Andrea , Prosdocimi Elena , Carrer Andrea , Checchetto Vanessa , Szabò Ildikò TITLE=Mitochondrial Ion Channels of the Inner Membrane and Their Regulation in Cell Death Signaling JOURNAL=Frontiers in Cell and Developmental Biology VOLUME=8 YEAR=2021 URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.620081 DOI=10.3389/fcell.2020.620081 ISSN=2296-634X ABSTRACT=

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.