complex III

Complex III, also known as ubiquinol-cytochrome c oxidoreductase or the cytochrome bc1 complex, is embedded in the inner mitochondrial membrane and functions in the electron transport chain (ETC). It accepts electrons from reduced ubiquinone (ubiquinol, CoQH2) generated by Complex I and Complex II, and passes them one at a time to cytochrome c via a mechanism called the Q cycle. This process involves two distinct binding sites (Qo and Qi) and results in the net translocation of protons (4 H+ per 2 electrons) from the mitochondrial matrix to the intermembrane space, contributing to the proton-motive force used by ATP synthase (Complex V) to generate ATP.

Complex III contains several key redox centers: cytochrome b (with bL and bH hemes), cytochrome c1, and the Rieske iron-sulfur protein (ISP). Electron flow through these centers is tightly coupled to proton pumping, making Complex III essential for oxidative phosphorylation.

Clinically, Complex III is a target of certain toxins and drugs. Antimycin A, a classic inhibitor used in biochemistry research, blocks electron transfer at the Qi site, halting the ETC and ATP production. Genetic mutations affecting Complex III subunits can cause mitochondrial diseases, often presenting with myopathy, encephalopathy, exercise intolerance, or multisystem dysfunction due to impaired oxidative phosphorylation. Complex III is also a significant source of reactive oxygen species (ROS), particularly at the Qo site, contributing to oxidative stress and implicated in aging and various pathologies.

For boards, know that Complex III sits between Complex I/II and Complex IV in the ETC, is inhibited by antimycin A, and its dysfunction leads to decreased ATP production and increased ROS generation, relevant to mitochondrial myopathies and cyanide-independent inhibition mechanisms (contrast with Complex IV inhibitors like cyanide and carbon monoxide).