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

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journal contribution
posted on 31.03.2021, 04:45 by JA Hayward, E Rajendran, SM Zwahlen, Pierre Faou, GG Van Dooren
© 2021 Hayward et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The mitochondrion is critical for the survival of apicomplexan parasites. Several major antiparasitic 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.

Funding

This work was supported by a Research School of Biology innovation grant to ER and GGvD, a National Health and Medical Research Council Ideas grant (GNT1182369) to GGvD, and an Australian Government Research Training Program Scholarship to JAH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

History

Publication Date

01/02/2021

Journal

PLoS Pathogens

Volume

17

Issue

2

Article Number

e1009211

Pagination

30p.

Publisher

Public Library of Science

ISSN

1553-7366

Rights Statement

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