FigureĀ 1.
The canonical electron transport chain (ETC) consists of four oxidoreductase complexes namely cI (NADH:ubiquinone oxidoreductase), cII (succinate:ubiquinone oxidoreductase), cIII (ubiquinol:cytochrome c oxidoreductase or the cytochrome bc1 complex) and cIV (cytochrome c oxidase).
The transfer of electrons from respiratory substrates at cI and cII to oxygen at cIV is coupled to proton translocation across the inner mitochondrial membrane (IM) at cI, cIII, and cIV generating a H+ electrochemical gradient which is the main driving force (protonmotive force, pmf) for ATP production at cV (mitochondrial F1F0-ATPase). This coupled process is hence termed oxidative phosphorylation (OXPHOS). Oxidation of respiratory substrates, generated by the TCA cycle (tricarboxylic acid cycle or Krebs cycle), maintains the TCA and keeps upstream metabolic circuits operational. The main functions of the ETC include maintenance of cellular redox balance, heat production, carbon turnover for biosynthetic purposes and ATP generation by OXPHOS. If cIII and/or cIV are impaired, electron flux through the ETC is stalled, causing an arrest of the TCA cycle and upstream metabolic cycles, as well as proton translocation. This leads to redox imbalance, ROS production and eventually decreases OXPHOS. AOX (alternative oxidase) restores electron flux through the ETC and thus most mitochondrial and metabolic functions even though cIII and cV are bypassed.