Mitochondrial respiratory chain complexes (Complexes I-V)

Mitochondrial respiratory chain complexes, also known as oxidative phosphorylation (OXPHOS) complexes I-V, are multienzyme assemblies embedded in the inner mitochondrial membrane that form the core of cellular energy production. They transfer electrons from NADH and FADH2 through a chain to oxygen, pumping protons to generate an electrochemical gradient that drives ATP synthesis by complex V (ATP synthase). Complex I (NADH:ubiquinone oxidoreductase) initiates the chain by oxidizing NADH and reducing ubiquinone while pumping protons; complex II (succinate dehydrogenase) feeds electrons from the TCA cycle; complex III (cytochrome bc1) and IV (cytochrome c oxidase) continue electron transfer and proton pumping; and complexes often assemble into respirasomes (supercomplexes) for efficient function and reduced ROS leakage. These complexes maintain redox balance but are major sites of reactive oxygen species (ROS) production when dysfunctional. Dysregulation impairs ATP production, elevates oxidative stress, and disrupts metabolism, contributing to diseases like neurodegenerative disorders (e.g., via complex I defects), liver pathologies (e.g., NAFLD, HCC), and cancer through bioenergetic failure and signaling alterations. While not typical monomeric drug targets like receptors or single enzymes, their subunits are implicated in mitochondrial diseases, with therapeutic interest in stabilizers or biogenesis modulators, though broad inhibition risks severe cytotoxicity due to universal energy dependence.

Other names

Oxidative phosphorylation (OXPHOS) complexeselectron transport chain (ETC) complexesrespiratory complexesrespirasomes (when assembled as supercomplexes)