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 apicomplexan genomes. 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 Plasmodium falciparum genome. This enzyme is rotenone insensitive [1, 2, 3, 4]. The orthologs of this enzyme are present in the Piroplasma species such as Theileria parva, Theileria annulata and Babesia bovis. The analysis of Piroplasma genomes shows the presence of only two sub units of succinate dehydrogenase (flavoprotein subunit and iron-sulphur protein subunits). The orthologs of the membrane anchor subunits have not been identified in these genomes. It was also the case with P. falciparum and Toxoplasma gondii genomes. Purification and molecular characterisation of the succinate dehydrogenase in P. falciparum has identified the above mentioned two subunits (flavoprotein subunit and iron-sulphur protein subunits)  and demonstrated significant activity. It is also suggested that this enzyme may be a peripheral complex [4, 5, 6].


The complex III of P. falciparum and T. gondii are similar to mammalian enzymes. The mammalian complex III inhibitors such as myxothiazol and antimycin A can inhibit Plasmodium complex III activity [4]. The differences in the ubiquinol binding regions of Plasmodium cytochrome b to mammalian protein has enabled the use of atovaquone as anti-malarial. Its action in complex III was confirmed by the study showing the resistance to atovoquone in malarial parasites with mutations in ubiquinol binding domains of cytochrome b [7]. The use of related drugs to treat East Coast Fever, an infection of T. parva [8] may suggest the conservation of ubiquinol binding domain of cytochrome b across Apicomplexa including these Piroplasma species. The genes for the two subunits of Cox2, the accessory protein Cox4 and the assembly proteins Cox10, Cox11, Cox12, Cox15, Cox17 and Cox19 are present in the nuclear genomes of these Piroplasma species. The Cox1 and Cox3 are present in the mitochondrial genomes of these species.


The Theileria and Babesia genomes possess the genes for all the F1 subunits and the Fo-c subunit (proteolipid subunit) of ATP synthase complex. The genes for Fo-a and Fo-b are not identified in these species as is the case with P. falciparum and T. gondii. It has been demonstrated in intra-erythrocytic stages of P. falciparum that electron transport chain does not play a role in ATP synthesis and it is only important for regeneration of ubiquinone as an electron acceptor for dihydroorotate dehydrogenase. It has also been proposed that the hydrolysis of ATP by matrix localised ATP synthase and transport of ADP for ATP will generate net negative charge and establishes membrane potential [9]. The presence of pyrimidine biosynthesis in Piroplasma suggests the role of this pathway in regeneration of ubiquinone. The role of this pathway in energy generation is yet to be confirmed in these species.


Enzyme EC Number Gene id Mitochondrial Complex
Glycerol-3-phosphate dehydrogenase TP01_0302  
Glycerol-3-phosphate dehydrogenase TP03_0730  
Malate:quinone oxidoreductase TP03_0758  
Ubiquinol cytochrome c oxidoreductase bc1 complex 14kDa subunit TP01_0860 Cytochrome bc1 complex (Complex III)
Ubiquinol cytochrome c oxidoreductase bc1 complex hinge protein TP04_0347 Cytochrome bc1 complex (Complex III)
Ubiquinol cytochrome c oxidoreductase bc1 complex Fe-S subunit TP04_0913 Cytochrome bc1 complex (Complex III)
Flavoprotein subunit of succinate dehydrogenase TP03_0230 Succinate dehydrogenase (ubiquinone) complex (Complex II)
Dihydroorotate dehydrogenase TP02_0171  
Iron-sulfur centres of succinate dehydrogenase TP01_0210 Succinate dehydrogenase (ubiquinone) complex (Complex II)
NAD(P)H dehydrogenase TP03_0539  
Cox2 TP01_0093 Cytochrome c oxidase (Complex IV)
Cox11 TP01_0104 Cytochrome c oxidase (Complex IV)
Cox12 TP01_0588 Cytochrome c oxidase (Complex IV)
Cox2 TP01_0683 Cytochrome c oxidase (Complex IV)
Cox19 TP01_0902 Cytochrome c oxidase (Complex IV)
Cox4 TP02_0045 Cytochrome c oxidase (Complex IV)
Cox15 TP03_0594 Cytochrome c oxidase (Complex IV)
Cox17 TP03_0837 Cytochrome c oxidase (Complex IV)
Cox10 TP04_0267 Cytochrome c oxidase (Complex IV)
Cox1 Tpmp1 (mitochondrial genome) Cytochrome c oxidase (Complex IV)
Cox3 Tpmp2 (mitochondrial genome) Cytochrome c oxidase (Complex IV)
ATP synthase gamma chain TP01_0201 ATP synthase (Complex V)
ATP synthase beta chain TP01_0389 ATP synthase (Complex V)
ATP synthase subunit O TP01_0929 ATP synthase (Complex V)
ATP synthase delta subunit TP02_0253 ATP synthase (Complex V)
ATP synthase lipid-binding protein (Fo-c subunit) TP02_0804 ATP synthase (Complex V)
ATP synthase epsilon chain TP03_0278 ATP synthase (Complex V)
ATP synthase alpha chain TP03_0569 ATP synthase (Complex V)
ATP synthase Fo-a subunit Missing in annotation ATP synthase (Complex V)
ATP synthase Fo-b subunit Missing in annotation ATP synthase (Complex V)
Cytochrome c none TP02_0396  
Cytochrome c1 none TP04_0384 Cytochrome bc1 complex (Complex III)
Cytochrome c none TP04_0712  
Cytochrome b none Tpmp3 (mitochondrial genome) Cytochrome bc1 complex (Complex III)


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Sources and fates of metabolites


Substrate Source pathways Product Fate pathways
Malate Tricarboxylic acid (TCA) cycle Oxaloacetate Tricarboxylic acid (TCA) cycle
L-dihydroorotate Pyrimidine metabolism Orotate Pyrimidine metabolism
Succinate Tricarboxylic acid (TCA) cycle Fumarate Tricarboxylic acid (TCA) cycle