A reaction to mitochondria in action

Abstract

In most cells and under most conditions, mitochondria produce the majority of the readily available energy (in the form of ATP) to sustain a myriad of biochemical processes necessary for the survival and proper function of the cell. Excitable cells, such as neurons and muscle cells, require very high amounts of ATP to maintain and restore the ion gradients across membranes as they experience frequent bouts of depolarization-induced Na+ and Ca2+ influx 1. Oxidative phosphorylation, the chemical process by which a high-energy phosphate bond is added to ADP to produce ATP, is mediated by electron transport chain (ETC) protein complex enzymes associated with the mitochondrial inner membrane (Figure 1). During the electron transport process superoxide anion radical (SO) is produced. Mitochondrial manganese superoxide dismutase (SOD) converts SO to the more stable and membrane permeable hydrogen peroxide, with the latter being converted to water via the actions of catalase and glutathione peroxidases. However, SO production can also lead to the generation of several highly destructive free radicals including hydroxyl radical and peroxynitrite 2. Excessive production and/or reduced detoxification of SO is implicated in the pathogenesis of a range of diseases including cardiovascular disease 3, diabetes 4 and neurodegenerative disorders 5. On the other hand, SO may serve as a signaling molecule that regulates cellular energy metabolism, growth and survival 6.