Mitochondrial Ion Channels: Gatekeepers of Life and Death

摘要

Continuous generation of ATP by mitochondrial oxidative phosphorylation is essential to maintain function in mechanically active cells such as cardiomyocytes. Emerging evidence indicates that mitochondrial ion channels activated by reactive oxygen species can induce a mitochondrial "critical" state, which can scale to cause electrical and contractile dysfunction of the cardiac cell and, ultimately, the whole heart. Here we focus on how mitochondrial ion channels participate in life-and-death decisions of the cell and discuss the challenges ahead for translating recent findings into novel therapeutic applications. We live in a dangerous environment, continuously immersed in a medium containing 21% oxygen, a highly reactive molecule. Fortunately for us, this impediment to life has been turned back on itself and has actually been harnessed by the cell to generate the stored chemical energy necessary to meet the major demands of cell physiology. Mitochondria are the organelles providing this protection, compartmentalizing and controlling the oxidation of metabolic fuels to produce ATR the high-energy phosphate used to maintain ion gradients, synthesize new molecules, actively dispose of old molecules, and perform mechanical work. In the heart, the energetic demands are extreme: the heart is required to pump roughly 75 gallons of blood per hour, unceasingly, for up to 100 years.