In addition to the three proton pumps in the supercomplex just discussed, one of the enzymes in the citric acid cycle, succinate dehydrogenase, is embedded in the mitochondrial crista membrane. In the course of oxidizing succinate to fumarate in the matrix, this enzyme complex captures electrons in the form of a tightly bound FADH2 molecule (see Panel 2–9, pp. 106–107) and passes them to
Figure 14–25The reaction of O2 with electrons in cytochrome c oxidase. Electrons from cytochrome c pass through the complex via bound copper ions (blue spheres)and hemes (red) to an O2 molecule bound between heme a3 and a copper ion. Iron ions are shown as red spheres. the iron atom in heme aserves as an electron queuing point where electrons are held so that they can be released to an O2 molecule (not shown) that is held at the bimetallic center active site, which is formed by the central iron of the other heme (heme a3) and a closely apposed copper atom. the four protons needed to reduce O2 to water are removed from the matrix. For each O2 molecule that undergoes the reaction 4e – + 4h+ + O2→ 2h2O, another four protons are pumped out of the matrix by mechanisms that are driven by allosteric changes in protein conformation (see Figure 14–28).
iron–sulfur cytochrome c Figure 14–26 The respiratory-chain mitochondria. the three proton-pumping CRISTA complexes of the mitochondrial respiratory chain of mammalian mitochondria assemble into large supercomplexes in the crista membrane. Supercomplexes can be isolated by mild detergent treatment of mitochondria, and their structure has been deciphered by single-particle cryoelectron microscopy. the bovine heart supercomplex has a total mass of 1.7 megadaltons. Shown is a schematic of such a complex that consists of NaDh dehydrogenase, cytochrome c reductase, and cytochrome c oxidase, as indicated. the facing quinol-binding sites of NaDh dehydrogenase and cytochrome c reductase, plus the short distance between the cytochrome c-binding sites in cytochrome c reductase and cytochrome c oxidase, facilitate fast, efficient electron transfer. Cofactors active in electron transport are marked as a yellow dot (flavin mononucleotide), red and yellow dots (iron–sulfur clusters), Q (quinone), red squares (hemes), and a blue dot (copper atom). Only cofactors participating in the linear flow of electrons from NaDh to water are shown. Blue arrows indicate the path of the electrons through the supercomplex. (adapted from t. athoff et al., EMBO J. 30:4652–4664, 2011.) a molecule of ubiquinone. The reduced ubiquinol then passes its two electrons to the respiratory chain via cytochrome c reductase (see Figure 14–18). Succinate dehydrogenase is not a proton pump, and it does not contribute directly to the electrochemical potential utilized for ATP production in mitochondria. Thus, it is not considered to be an integral part of the respiratory chain.