InterPro domain: IPR038659

The alternative oxidase (AOX) is an enzyme that forms part of the electron transport chain in mitochondria of different organisms [ 1 , 2 ]. Proteins homologous to the mitochondrial oxidase have also been identified in bacterial genomes [ 3 , 4 ]. The oxidase provides an alternative route for electrons passing through the electron transport chain to reduce oxygen. However, as several proton-pumping steps are bypassed in this alternative pathway, activation of the oxidase reduces ATP generation. This enzyme was first identified as a distinct oxidase pathway from cytochrome c oxidase as the alternative oxidase is resistant to inhibition by the poison cyanide [ 5 ].

The alternative oxidase (also known as ubiquinol oxidase) is used as a second terminal oxidase in the mitochondria, electrons are transferred directly from reduced ubiquinol to oxygen forming water [ 6 ]. This is not coupled to ATP synthesis and is not inhibited by cyanide, this pathway is a single step process [ 7 ]. In Oryza sativa (rice) the transcript levels of the alternative oxidase are increased by low temperature [ 8 ]. It has been predicted to contain a coupled diiron centre on the basis of a conserved sequence motif consisting of the proposed iron ligands, four Glu and two His residues [ 8 ]. The EPR study of Arabidopsis thaliana (mouse-ear cress) alternative oxidase AOX1a shows that the enzyme contains a hydroxo-bridged mixed-valent Fe(II)/Fe(III) binuclear iron centre [ 9 ]. A catalytic cycle has been proposed that involves a di-iron centre and at least one transient protein-derived radical, most probably an invariant Tyr residue [ 10 ].

The structure of alternative oxidase from Trypanosoma brucei has been solved. The enzyme is a homodimer with the nonhaem di-iron carboxylate active site buried within a four-helix bundle. In the inhibitor-free state, the di-iron carboxylate is ligated by four glutamate residues, but on binding of an inhibitor, a histidine is also induced to act as a ligand. A highly conserved tyrosine is close to the active site and required for activity [ 11 ]. This entry represents proteins with a structure similar to that of alternative oxidase.

1. Branched mitochondrial electron transport in the Animalia: presence of alternative oxidase in several animal phyla. IUBMB Life 56, 333-41
2. Alternative oxidase in the branched mitochondrial respiratory network: an overview on structure, function, regulation, and role. Braz. J. Med. Biol. Res. 31, 733-47
3. Prokaryotic orthologues of mitochondrial alternative oxidase and plastid terminal oxidase. Plant Mol. Biol. 53, 865-76
4. Identification of prokaryotic homologues indicates an endosymbiotic origin for the alternative oxidases of mitochondria (AOX) and chloroplasts (PTOX). Gene 330, 143-8
5. The regulation and nature of the cyanide-resistant alternative oxidase of plant mitochondria. Biochim. Biophys. Acta 1059, 121-40
6. Cloning and analysis of the alternative oxidase gene of Neurospora crassa. Genetics 142, 129-40
7. Transcript levels of tandem-arranged alternative oxidase genes in rice are increased by low temperature. Gene 203, 121-9
8. New insight into the structure and function of the alternative oxidase. Biochim. Biophys. Acta 1460, 241-54
9. EPR studies of the mitochondrial alternative oxidase. Evidence for a diiron carboxylate center. J. Biol. Chem. 277, 43608-14
10. Exploring the molecular nature of alternative oxidase regulation and catalysis. FEBS Lett. 510, 121-6
11. Structure of the trypanosome cyanide-insensitive alternative oxidase. Proc. Natl. Acad. Sci. U.S.A. 110, 4580-5