Complexome profile of Toxoplasma gondii mitochondria identifies divergent subunits of respiratory chain complexes including new subunits of cytochrome bc1 complex
Year: 2021
Type: article
Abstract: The mitochondrial electron transport chain (mETC) and F 1 F o -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 F 1 F o -ATP synthase. We identified and assigned 60 proteins to complexes II, IV and F 1 F o -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 role as complex III subunits. Our study highlights the divergent subunit composition of the apicomplexan mETC complexes and sets the stage for future structural and drug discovery studies. Author Summary Apicomplexan parasites, such as Toxoplasma and Plasmodium , cause diseases of global importance, such as toxoplasmosis and malaria. The mitochondrial electron transport chain (mETC) and F 1 F o -ATP synthase, which provide the parasite with energy and important metabolites, are essential for parasite function. Here, using a proteomic technique called complexome profiling, we report the composition of the Toxoplasma mETC and F 1 F o -ATP synthase. In particular, we reveal the compositions of complexes II and III for the first time. Complex III is an important drug target, yet its full protein composition was unknown. We identify new parasite-specific complex III subunits and demonstrate that they are essential for parasite survival and for proper functioning of the mETC. Our study highlights the divergent nature of the apicomplexan mETC and F 1 F o -ATP synthase.
Source: PLoS Pathogens
Language: English
Subfield: Parasitology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,575
Funders: Wellcome Trust, International Seafood Sustainability Foundation, Royal Society of Edinburgh, University of Glasgow, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Hebrew University of Jerusalem, Directorate for Biological Sciences, Medical Research Council, Biotechnology and Biological Sciences Research Council
Awards: G1257286180, Identification and functional characterization of proteins of the mitochondrial tRNA import pathway of Toxoplasma gondii, G29316538, Investigation of the function of the ER/mitochondria contact sites in cell physiology and disease, G5696642649, University of Glasgow UKRI Innovation Fellowships: BBSRC Flexible Talent Mobility Accounts, Elucidating the structure and function of the divergent and essential cytochrome bc1 complex in apicomplexan parasites, Lost in translation. Dissecting the divergent features of Toxoplasma gondii mitochondrial translation
OpenAlex ID: W3135549026