Electron transport chain
A continuous supply of energy in the form of ATP is essential to the maintenance of life. In most eukaryotes, it is achieved by oxygen-dependent energy production and mitochondrial electron transport chain plays central role in ATP production. In higher eukaryotes, electron transport chain comprises four integral membrane protein complexes namely, NADH:ubiquinone oxidoreductase (complex I), succinate:ubiquinone oxidoreductase (complex II), ubiquinol:cytochrome c oxidoreductase/ cytochrome bc1 complex (complex III) and cytochrome oxidase (complex IV). The electrons are transferred from NADH and succinate to oxygen through these series of enzymatic complexes of the inner mitochondrial membrane and oxygen is reduced to water. This releases energy and generates a proton gradient across mitochondrial membrane by pumping protons into intermembrane space. The energy of oxidation of hydrogen is used to phosphorylate ADP into ATP. This ATP generation is catalysed by ATP synthase complex (complex V).
The conventional NADH:ubiquinone oxidoreductase multiprotein complex is absent in the genomes of Plasmodium falciparum, Toxoplasma gondii and Cryptosporidium species. However, an alternative single gene NAD(P)H dehydrogenase enzyme homologous to the peripheral membrane NADH dehydrogenase in yeast, plants and fungi was identified in P. falciparum genome. These alternative NADH dehydrogenases of mitochondrial membrane are insensitive to rotenone, an inhibitor of complex I . The presence of oxidation of exogenous NADH and its insensitivity to rotenone has been experimentally shown in P. falciparum and Plasmodium yoelii yoelii. This confirms the presence of alternative NADH dehydrogenase in these species [2, 3, 4]. The analysis of Cryptosporidium genomes has showed that they also possess NAD(P)H dehydrogenase which are orthologous to the Plasmodium alternative NAD(P)H dehydrogenase.
The analysis of the genome of Cryptosporidium muris shows the presence of only two subunits of succinate dehydrogenase (flavoprotein subunit and iron-sulphur protein subunits). The homologs of the membrane anchor subunits have not been identified in the C. muris genome as in P. falciparum and T. gondii genomes. The complex III and complex IV are absent in the genomes of Cryptosporidium species. They possess a single gene alternative ubiquinol oxidase (AOX). The cloning and expression of Cryptosporidium parvum AOX gene and the inhibition of growth with inhibitors SHAM and 8-hydroxyquinoline has confirmed the presence of alternative oxidase function in Cryptosporidium species . The C. muris genome possesses the genes for F1 subunits and the Fo-c subunit (proteolipid subunit) of ATP synthase. The genes for Fo-a and Fo-b are not identified in these species as in P. falciparum and T. gondii [4, 6]. Although Fo-a and Fo-b subunits of ATP synthase are missing in T. gondii , it has been demonstrated that electron transport chain mediated generation of ATP is essential for T. gondii .
|Enzyme||EC Number||Gene id||Mitochondrial Complex|
|Alternative oxidase (ubiquinol oxidase)||126.96.36.199||CMU_000270|
|Flavoprotein subunit of succinate dehydrogenase||188.8.131.52||CMU_043190||Succinate dehydrogenase (ubiquinone) complex (Complex II)|
|Iron-sulfur centres of succinate dehydrogenase||184.108.40.206||CMU_014010||Succinate dehydrogenase (ubiquinone) complex (Complex II)|
|ATP synthase epsilon chain||220.127.116.11||CMU_002850||ATP synthase (Complex V)|
|ATP synthase beta chain||18.104.22.168||CMU_008950||ATP synthase (Complex V)|
|ATP synthase delta subunit||22.214.171.124||CMU_008960||ATP synthase (Complex V)|
|ATP synthase F0-lipid binding domain||126.96.36.199||CMU_016520||ATP synthase (Complex V)|
|ATP synthase gamma chain||188.8.131.52||CMU_017340||ATP synthase (Complex V)|
|ATP synthase subunit O||184.108.40.206||CMU_025000||ATP synthase (Complex V)|
|ATP synthase alpha chain||220.127.116.11||CMU_027630||ATP synthase (Complex V)|
|ATP synthase Fo-a subunit||18.104.22.168||Missing in annotation||ATP synthase (Complex V)|
|ATP synthase Fo-b subunit||22.214.171.124||Missing in annotation||ATP synthase (Complex V)|