FIGURE 12-22 The mitochondrial electron-transport chain. Electrons (blue arrows) flow through four major multiprotein complexes (I–IV). Electron movement between complexes is mediated either by the lipid-soluble molecule coenzyme Q (CoQ, oxidized form; CoQH₂, reduced form) or the water-soluble protein cytochrome c (cyt c). Three of the multiprotein complexes use the energy released from the electrons to pump protons (red arrows) from the matrix (cytosolic compartment in bacteria) to the intermembrane space (exoplasmic space of bacteria). (a) Pathway from NADH. Electrons from NADH (2/NADH oxidized) flow through complex I, initially via a flavin mononucleotide (FMN) and then sequentially via seven iron-sulfur clusters (Fe-S), to CoQ, to which two protons bind, forming CoQH₂. Conformational changes in complex I that accompany the electron flow drive proton pumping from the matrix to the intramembrane space. Electrons then flow via the released (and subsequently recycled) CoQH₂ to complex III, and then via cyt c to complex IV. Each of four cyt c molecules carrying four electrons originating from two NADHs transfers individual electrons to complex IV for the four-electron reduction of one O₂ molecule to two H₂O molecules and transport of four protons. Thus, for every two NADHs oxidized and one O₂ molecule reduced, a total of 20 protons are translocated out of the matrix into the intermembrane space. (b) Pathway from succinate. Two electrons flow from each succinate to complex II via FAD/FADH₂ and iron-sulfur clusters (Fe-S), from complex II to complex III via CoQ/CoQH₂, and then to complex IV via cyt c. Electrons released during oxidation of succinate to fumarate in complex II are used to reduce CoQ to CoQH₂ without translocating additional protons. The remainder of electron transport from CoQH₂ proceeds by the same pathway as for the NADH pathway in (a). Thus, for every two succinates oxidized and one O₂ molecule reduced,12 protons (8 via the Q-cycle of complex III, 4 via complex IV) are translocated.