Alternative oxidase

The alternative oxidase is an enzyme that forms part of the electron transport chain in plants, as well as some fungi, protists and possibly some animals. [cite journal |author=McDonald A, Vanlerberghe G |title=Branched mitochondrial electron transport in the Animalia: presence of alternative oxidase in several animal phyla |journal=IUBMB Life |volume=56 |issue=6 |pages=333–41 |year=2004 |pmid=15370881 |doi=10.1080/1521-6540400000876] [cite journal |author=Sluse FE, Jarmuszkiewicz W |title=Alternative oxidase in the branched mitochondrial respiratory network: an overview on structure, function, regulation, and role |journal=Braz. J. Med. Biol. Res. |volume=31 |issue=6 |pages=733–47 |year=1998 |pmid=9698817 |doi=10.1590/S0100-879X1998000600003] Sequences similar to the plant oxidase have also been identified in bacterial genomes. [cite journal |author=McDonald AE, Amirsadeghi S, Vanlerberghe GC |title=Prokaryotic orthologues of mitochondrial alternative oxidase and plastid terminal oxidase |journal=Plant Mol. Biol. |volume=53 |issue=6 |pages=865–76 |year=2003 |pmid=15082931 |doi=10.1023/B:PLAN.0000023669.79465.d2] [cite journal |author=Atteia A, van Lis R, van Hellemond JJ, Tielens AG, Martin W, Henze K |title=Identification of prokaryotic homologues indicates an endosymbiotic origin for the alternative oxidases of mitochondria (AOX) and chloroplasts (PTOX) |journal=Gene |volume=330 |issue= |pages=143–8 |year=2004 |pmid=15087133 |doi=10.1016/j.gene.2004.01.015]

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. [cite journal |author=Moore AL, Siedow JN |title=The regulation and nature of the cyanide-resistant alternative oxidase of plant mitochondria |journal=Biochim. Biophys. Acta |volume=1059 |issue=2 |pages=121–40 |year=1991 |pmid=1883834 |doi=10.1016/S0005-2728(05)80197-5]

Function

This metabolic pathway leading to the alternative oxidase diverges from the cytochrome-linked electron transport chain at the ubiquinone pool. [cite journal |author=Juszczuk IM, Rychter AM |title=Alternative oxidase in higher plants |url=http://www.actabp.pl/pdf/4_2003/1257.pdf |journal=Acta Biochim. Pol. |volume=50 |issue=4 |pages=1257–71 |year=2003 |pmid=14740012] 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. [cite journal |author=Vanlerberghe GC, McIntosh L |title=Alternative oxidase: From Gene to Function |journal= |volume=48 |issue= |pages=703–734 |year=1997 |pmid=15012279 |doi=10.1146/annurev.arplant.48.1.703] [cite journal |author=Ito Y, Saisho D, Nakazono M, Tsutsumi N, Hirai A |title=Transcript levels of tandem-arranged alternative oxidase genes in rice are increased by low temperature |journal=Gene |volume=203 |issue=2 |pages=121–9 |year=1997 |pmid=9426242 |doi=10.1016/S0378-1119(97)00502-7] Although the benefit conferred by this activity remains uncertain, it may enhance an organisms' ability to resist these stresses, through reducing the level of oxidative stress. [cite journal |author=Maxwell DP, Wang Y, McIntosh L |title=The alternative oxidase lowers mitochondrial reactive oxygen production in plant cells |url=http://www.pnas.org/cgi/content/full/96/14/8271 |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=96 |issue=14 |pages=8271–6 |year=1999 |pmid=10393984 |doi=10.1073/pnas.96.14.8271]

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. [cite journal |author=Chaudhuri M, Ott RD, Hill GC |title=Trypanosome alternative oxidase: from molecule to function |journal=Trends Parasitol. |volume=22 |issue=10 |pages=484–91 |year=2006 |pmid=16920028 |doi=10.1016/j.pt.2006.08.007] [cite journal |author=Clarkson AB, Bienen EJ, Pollakis G, Grady RW |title=Respiration of bloodstream forms of the parasite Trypanosoma brucei brucei is dependent on a plant-like alternative oxidase |url=http://www.jbc.org/cgi/reprint/264/30/17770.pdf |journal=J. Biol. Chem. |volume=264 |issue=30 |pages=17770–6 |year=1989 |pmid=2808350] This major metabolic difference between the parasite and its human host has made the "T. brucei" alternative oxidase an attractive target for drug design. [cite journal |author=Nihei C, Fukai Y, Kita K |title=Trypanosome alternative oxidase as a target of chemotherapy |journal=Biochim. Biophys. Acta |volume=1587 |issue=2-3 |pages=234–9 |year=2002 |pmid=12084465] [cite journal |author=Grady RW, Bienen EJ, Dieck HA, Saric M, Clarkson AB |title=N-n-alkyl-3,4-dihydroxybenzamides as inhibitors of the trypanosome alternative oxidase: activity in vitro and in vivo |url=http://aac.asm.org/cgi/reprint/37/5/1082.pdf |journal=Antimicrob. Agents Chemother. |volume=37 |issue=5 |pages=1082–5 |year=1993 |pmid=8517695] Of the known inhibitors of alternative oxidases, the antibiotic ascofuranone inhibits the "T. brucei" enzyme and cures infection in mice. [cite journal |author=Minagawa N, Yabu Y, Kita K, Nagai K, Ohta N, Meguro K, Sakajo S, Yoshimoto A |title=An antibiotic, ascofuranone, specifically inhibits respiration and in vitro growth of long slender bloodstream forms of Trypanosoma brucei brucei |journal=Mol. Biochem. Parasitol. |volume=84 |issue=2 |pages=271–80 |year=1997 |pmid=9084049 |doi=10.1016/S0166-6851(96)02797-1] [cite journal |author=Yabu Y, Yoshida A, Suzuki T, Nihei C, Kawai K, Minagawa N, Hosokawa T, Nagai K, Kita K, Ohta N |title=The efficacy of ascofuranone in a consecutive treatment on Trypanosoma brucei brucei in mice |journal=Parasitol. Int. |volume=52 |issue=2 |pages=155–64 |year=2003 |pmid=12798927 |doi=10.1016/S1383-5769(03)00012-6]

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. [cite journal |author=Miguez M, Reeve C, Wood PM, Hollomon DW |title=Alternative oxidase reduces the sensitivity of Mycosphaerella graminicola to QOI fungicides |journal=Pest Manag. Sci. |volume=60 |issue=1 |pages=3–7 |year=2004 |pmid=14727735 |doi=10.1002/ps.837] However, as the alternative pathway generates less ATP, these fungicides are still effective in preventing spore germination, as this is an energy-intensive process. [cite journal |author=Avila-Adame C, Köller W |title=Impact of alternative respiration and target-site mutations on responses of germinating conidia of Magnaporthe grisea to Qo-inhibiting fungicides |journal=Pest Manag. Sci. |volume=59 |issue=3 |pages=303–9 |year=2003 |pmid=12639047 |doi=10.1002/ps.638]

tructure and mechanism

The alternative oxidase is a integral membrane protein that is tightly bound to the inner mitochondrial membrane. [cite journal |author=Berthold DA, Stenmark P |title=Membrane-bound diiron carboxylate proteins |journal=Annual review of plant biology |volume=54 |issue= |pages=497–517 |year=2003 |pmid=14503001 |doi=10.1146/annurev.arplant.54.031902.134915] 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 glutamine and two histidine amino acid residues. [cite journal |author=Berthold DA, Andersson ME, Nordlund P |title=New insight into the structure and function of the alternative oxidase |journal=Biochim. Biophys. Acta |volume=1460 |issue=2-3 |pages=241–54 |year=2000 |pmid=11106766 |doi=10.1016/S0005-2728(00)00149-3] 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. [cite journal |author=Berthold DA, Voevodskaya N, Stenmark P, Gräslund A, Nordlund P |title=EPR studies of the mitochondrial alternative oxidase. Evidence for a diiron carboxylate center |url=http://www.jbc.org/cgi/content/full/277/46/43608 |journal=J. Biol. Chem. |volume=277 |issue=46 |pages=43608–14 |year=2002 |pmid=12215444 |doi=10.1074/jbc.M206724200] 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 an invariant tyrosine residue. [cite journal |author=Affourtit C, Albury MS, Crichton PG, Moore AL |title=Exploring the molecular nature of alternative oxidase regulation and catalysis |journal=FEBS Lett. |volume=510 |issue=3 |pages=121–6 |year=2002 |pmid=11801238 |doi=10.1016/S0014-5793(01)03261-6]

ee also

* Metalloprotein
* Bioinorganic chemistry
* Cofactor

References

External links

* [http://www.chem.qmul.ac.uk/iubmb/etp/etp1t3.html Electron transport proteins]
* [http://www.ebi.ac.uk/interpro/DisplayIproEntry?ac=IPR002680 InterPro entry on alternative oxidases]
*
* [http://www.tau.ac.il/~ecology/virtau/2-elitsur/ey.htm#AlternativeRespiration Alternative respiration] Root Research Introduction Virtual Course Seminar

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