Biology:Alternative oxidase

From HandWiki
The alternative oxidase shown as part of the complete electron transport chain. UQ is ubiquinol/ubiquinone, C is cytochrome c and AOX is the alternative oxidase.
Alternative oxidase
Identifiers
SymbolAOX
PfamPF01786
InterProIPR002680
OPM superfamily357
OPM protein3w54
Also matches plastid terminal oxidase and bacterial AOX.

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 and the related plastid terminal 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]

Function

The fungicide azoxystrobin.

This metabolic pathway leading to the alternative oxidase diverges from the cytochrome-linked electron transport chain at the ubiquinone pool.[6] Alternative pathway respiration only produces proton translocation at Complex 1 (NADH dehydrogenase) and so has a lower ATP yield than the full pathway. The expression of the alternative oxidase gene AOX is influenced by stresses such as cold, reactive oxygen species and infection by pathogens, as well as other factors that reduce electron flow through the cytochrome pathway of respiration.[7][8] Although the benefit conferred by this activity remains uncertain, it may enhance an organism's ability to resist these stresses by maintaining the oxidized state of the upstream electron-transport components, thereby reducing the level of oxidative stress induced by overreduced electron carriers.[9]

Unusually, the bloodstream form of the protozoan parasite Trypanosoma brucei, which is the cause of sleeping sickness, depends entirely on the alternative oxidase pathway for cellular respiration through its electron transport chain.[10][11] This major metabolic difference between the parasite and its human host has made the T. brucei alternative oxidase an attractive target for drug design.[12][13] Of the known inhibitors of alternative oxidases, the antibiotic ascofuranone inhibits the T. brucei enzyme and cures infection in mice.[14][15]

In fungi, the ability of the alternative oxidase to bypass inhibition of parts of the electron transport chain can contribute to fungicide resistance. This is seen in the strobilurin fungicides that target complex III, such as azoxystrobin, picoxystrobin and fluoxastrobin.[16] However, even though the alternative pathway generates less ATP, these fungicides are still effective in preventing spore germination, as this is an energy-intensive process.[17]

Structure and mechanism

The alternative oxidase is an integral monotopic membrane protein that is tightly bound to the inner mitochondrial membrane from matrix side[18] The enzyme has been predicted to contain a coupled diiron center on the basis of a conserved sequence motif consisting of the proposed iron ligands, four glutamate and two histidine amino acid residues.[19] The electron spin resonance study of Arabidopsis thaliana alternative oxidase AOX1a showed that the enzyme contains a hydroxo-bridged mixed-valent Fe(II)/Fe(III) binuclear iron center.[20] A catalytic cycle has been proposed that involves this di-iron center and at least one transient protein-derived free radical, which is probably formed on a tyrosine residue.[21]

See also

References

  1. ↑ "Branched mitochondrial electron transport in the Animalia: presence of alternative oxidase in several animal phyla". IUBMB Life 56 (6): 333–41. 2004. doi:10.1080/1521-6540400000876. PMID 15370881. 
  2. ↑ "Alternative oxidase in the branched mitochondrial respiratory network: an overview on structure, function, regulation, and role". Braz. J. Med. Biol. Res. 31 (6): 733–47. 1998. doi:10.1590/S0100-879X1998000600003. PMID 9698817. 
  3. ↑ "Prokaryotic orthologues of mitochondrial alternative oxidase and plastid terminal oxidase". Plant Mol. Biol. 53 (6): 865–76. 2003. doi:10.1023/B:PLAN.0000023669.79465.d2. PMID 15082931. 
  4. ↑ "Identification of prokaryotic homologues indicates an endosymbiotic origin for the alternative oxidases of mitochondria (AOX) and chloroplasts (PTOX)". Gene 330: 143–8. 2004. doi:10.1016/j.gene.2004.01.015. PMID 15087133. 
  5. ↑ "The regulation and nature of the cyanide-resistant alternative oxidase of plant mitochondria". Biochim. Biophys. Acta 1059 (2): 121–40. 1991. doi:10.1016/S0005-2728(05)80197-5. PMID 1883834. 
  6. ↑ "Alternative oxidase in higher plants". Acta Biochim. Pol. 50 (4): 1257–71. 2003. doi:10.18388/abp.2003_3649. PMID 14740012. http://www.actabp.pl/pdf/4_2003/1257.pdf. 
  7. ↑ "Alternative oxidase: From Gene to Function". Annual Review of Plant Physiology and Plant Molecular Biology 48: 703–734. 1997. doi:10.1146/annurev.arplant.48.1.703. PMID 15012279. 
  8. ↑ "Transcript levels of tandem-arranged alternative oxidase genes in rice are increased by low temperature". Gene 203 (2): 121–9. 1997. doi:10.1016/S0378-1119(97)00502-7. PMID 9426242. 
  9. ↑ "The alternative oxidase lowers mitochondrial reactive oxygen production in plant cells". Proc. Natl. Acad. Sci. U.S.A. 96 (14): 8271–6. 1999. doi:10.1073/pnas.96.14.8271. PMID 10393984. Bibcode: 1999PNAS...96.8271M. 
  10. ↑ "Trypanosome alternative oxidase: from molecule to function". Trends Parasitol. 22 (10): 484–91. 2006. doi:10.1016/j.pt.2006.08.007. PMID 16920028. 
  11. ↑ "Respiration of bloodstream forms of the parasite Trypanosoma brucei brucei is dependent on a plant-like alternative oxidase". J. Biol. Chem. 264 (30): 17770–6. 1989. doi:10.1016/S0021-9258(19)84639-2. PMID 2808350. 
  12. ↑ "Trypanosome alternative oxidase as a target of chemotherapy". Biochim. Biophys. Acta 1587 (2–3): 234–9. 2002. doi:10.1016/s0925-4439(02)00086-8. PMID 12084465. 
  13. ↑ "N-n-alkyl-3,4-dihydroxybenzamides as inhibitors of the trypanosome alternative oxidase: activity in vitro and in vivo". Antimicrob. Agents Chemother. 37 (5): 1082–5. 1993. doi:10.1128/aac.37.5.1082. PMID 8517695. 
  14. ↑ "An antibiotic, ascofuranone, specifically inhibits respiration and in vitro growth of long slender bloodstream forms of Trypanosoma brucei brucei". Mol. Biochem. Parasitol. 84 (2): 271–80. 1997. doi:10.1016/S0166-6851(96)02797-1. PMID 9084049. 
  15. ↑ "The efficacy of ascofuranone in a consecutive treatment on Trypanosoma brucei brucei in mice". Parasitol. Int. 52 (2): 155–64. 2003. doi:10.1016/S1383-5769(03)00012-6. PMID 12798927. 
  16. ↑ "Alternative oxidase reduces the sensitivity of Mycosphaerella graminicola to QOI fungicides". Pest Manag. Sci. 60 (1): 3–7. 2004. doi:10.1002/ps.837. PMID 14727735. 
  17. ↑ "Impact of alternative respiration and target-site mutations on responses of germinating conidia of Magnaporthe grisea to Qo-inhibiting fungicides". Pest Manag. Sci. 59 (3): 303–9. 2003. doi:10.1002/ps.638. PMID 12639047. 
  18. ↑ "Membrane-bound diiron carboxylate proteins". Annual Review of Plant Biology 54: 497–517. 2003. doi:10.1146/annurev.arplant.54.031902.134915. PMID 14503001. 
  19. ↑ "New insight into the structure and function of the alternative oxidase". Biochim. Biophys. Acta 1460 (2–3): 241–54. 2000. doi:10.1016/S0005-2728(00)00149-3. PMID 11106766. 
  20. ↑ "EPR studies of the mitochondrial alternative oxidase. Evidence for a diiron carboxylate center". J. Biol. Chem. 277 (46): 43608–14. 2002. doi:10.1074/jbc.M206724200. PMID 12215444. 
  21. ↑ "Exploring the molecular nature of alternative oxidase regulation and catalysis". FEBS Lett. 510 (3): 121–6. 2002. doi:10.1016/S0014-5793(01)03261-6. PMID 11801238. 

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