Divergent features of the coenzyme Q:cytochrome c oxidoreductase complex in Toxoplasma gondii parasites

The mitochondrion is critical for the survival of apicomplexan parasites. Several major anti-parasitic drugs, such as atovaquone and endochin-like quinolones, act through inhibition of the mitochondrial electron transport chain at the coenzyme Q:cytochrome c oxidoreductase complex (Complex III). Des...

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Bibliographic Details
Published in:PLoS pathogens 2021-02, Vol.17 (2), p.e1009211-e1009211
Main Authors: Hayward, Jenni A, Rajendran, Esther, Zwahlen, Soraya M, Faou, Pierre, van Dooren, Giel G
Format: Article
Language:English
Subjects:
Amino acid sequence
Animals
Antibodies
Biology and Life Sciences
Blotting, Western
Cells, Cultured
Coenzyme Q
Cryptosporidium
Cytochrome
Cytochrome-c oxidase
Cytochromes
Deoxyribonucleic acid
Divergence
DNA
Electron Transport Complex III - chemistry
Electron Transport Complex III - metabolism
Expected values
Experiments
Fluorescent Antibody Technique
Genomes
Homology
Humans
Malaria
Mass spectrometry
Mass spectroscopy
Mitochondria
Mitochondria - metabolism
Oxidoreductase
Oxygen - metabolism
Parasites
Protein Subunits - chemistry
Protein Subunits - metabolism
Proteins
Protozoa
Pseudogenes
Research and analysis methods
Scientific imaging
Smegmamorpha
Toxoplasma - genetics
Toxoplasma - metabolism
Toxoplasma gondii
Toxoplasmosis
Vector-borne diseases
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Summary:The mitochondrion is critical for the survival of apicomplexan parasites. Several major anti-parasitic drugs, such as atovaquone and endochin-like quinolones, act through inhibition of the mitochondrial electron transport chain at the coenzyme Q:cytochrome c oxidoreductase complex (Complex III). Despite being an important drug target, the protein composition of Complex III of apicomplexan parasites has not been elucidated. Here, we undertake a mass spectrometry-based proteomic analysis of Complex III in the apicomplexan Toxoplasma gondii. Along with canonical subunits that are conserved across eukaryotic evolution, we identify several novel or highly divergent Complex III components that are conserved within the apicomplexan lineage. We demonstrate that one such subunit, which we term TgQCR11, is critical for parasite proliferation, mitochondrial oxygen consumption and Complex III activity, and establish that loss of this protein leads to defects in Complex III integrity. We conclude that the protein composition of Complex III in apicomplexans differs from that of the mammalian hosts that these parasites infect.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1009211