title: The malaria parasite type II NADH:quinone oxidoreductase: an alternative enzyme for an alternative lifestyle.
abstract: The operation of a type II NADH:quinone oxidoreductase (PfNDH2), also known as alternative Complex I, in the mitochondrion of the human malaria parasite, Plasmodium falciparum, has recently been described. Unlike the Complex I of typical mitochondria, type II NADH:quinone oxidoreductases do not have transmembrane domains and are not involved directly in proton (H(+)) pumping. Here, we present a predictive model of PfNDH2, describing putative NADH-, flavin- and quinone-binding sites, as well as a possible membrane 'anchoring' region. In addition, we hypothesize that the alternative Complex I is an evolutionary adaptation to a microaerophilic lifestyle enabling (proton) uncoupled oxidation of NADH. This adaptive feature has several advantages, including: (i) a reduction of proton 'back-pressure' in the absence of extensive ATP synthesis; (ii) a reduction of mitochondrial superoxide generation; and (iii) a mechanism for the deregulated oxidation of cytosolic NADH.
authors.affiliation: Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Fisher
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Bray
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Ward
authors.forename: Giancarlo A
authors.initials: GA
authors.lastname: Biagini
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D019143:Evolution, Molecular; D008928:Mitochondria / Q000201:enzymology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009247:NADH, NADPH Oxidoreductases / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D010963:Plasmodium falciparum / Q000201:enzymology*; D011809:Quinones / Q000378:metabolism*
chemical_list: D011809:Quinones; D009247:NADH, NADPH Oxidoreductases