Complexome profile of Toxoplasma gondii mitochondria identifies divergent subunits of respiratory chain complexes including new subunits of cytochrome bc1 complex

Maclean, A. E., Bridges, H. R., F. Silva, M., Ding, S., Ovciarikova, J., Hirst, J. and Sheiner, L. (2021) Complexome profile of Toxoplasma gondii mitochondria identifies divergent subunits of respiratory chain complexes including new subunits of cytochrome bc1 complex. PLoS Pathogens, 17(3), e1009301. (doi: 10.1371/journal.ppat.1009301) (PMID:33651838) (PMCID:PMC7987180)

Abstract

The mitochondrial electron transport chain (mETC) and F1Fo-ATP synthase are of central importance for energy and metabolism in eukaryotic cells. The Apicomplexa, important pathogens of humans causing diseases such as toxoplasmosis and malaria, depend on their mETC in every known stage of their complicated life cycles. Here, using a complexome profiling proteomic approach, we have characterised the Toxoplasma mETC complexes and F1Fo-ATP synthase. We identified and assigned 60 proteins to complexes II, IV and F1Fo-ATP synthase of Toxoplasma, of which 16 have not been identified previously. Notably, our complexome profile elucidates the composition of the Toxoplasma complex III, the target of clinically used drugs such as atovaquone. We identified two new homologous subunits and two new parasite-specific subunits, one of which is broadly conserved in myzozoans. We demonstrate all four proteins are essential for complex III stability and parasite growth, and show their depletion leads to decreased mitochondrial potential, supporting their assignment as complex III subunits. Our study highlights the divergent subunit composition of the apicomplexan mETC and F1Fo-ATP synthase complexes and sets the stage for future structural and drug discovery studies.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Ferreira Silva, Miss Mariana and Ovciarikova, Miss Jana and MacLean, Dr Andrew and Sheiner, Professor Lilach

Creator Roles

Maclean, A. E.: Conceptualization, Data curation, Funding acquisition, Investigation, Methodology, Writing – original draft, Writing – review and editing
Ovciarikova, J.: Formal analysis, Investigation
Sheiner, L.: Conceptualization, Data curation, Funding acquisition, Methodology, Supervision, Writing – original draft

• Authors: Maclean, A. E., Bridges, H. R., F. Silva, M., Ding, S., Ovciarikova, J., Hirst, J., and Sheiner, L.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: PLoS Pathogens
• Publisher: Public Library of Science
• ISSN: 1553-7366
• ISSN (Online): 1553-7374
• Published Online: 02 March 2021
• Copyright Holders: Copyright © 2021 Maclean et al.
• First Published: First published in PLoS Pathogens 17(3): e1009301
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
172187		Dissection of the unusual mitochondrial tRNA import translocon of Toxoplasma gondii	Lilach Sheiner	Biotechnology and Biological Sciences Research Council (BBSRC)	BB/N003675/1	Institute of Infection, Immunity & Inflammation
307056		Lost in translation. A study of the divergent mitochondrial translation pathway of the parasite Toxoplasma gondii	Lilach Sheiner	Wellcome Trust (WELLCOTR)	217173/Z/19/Z	MVLS - Polyomics Facility