Open AccessComplexome profile of Toxoplasma gondii mitochondria identifies divergent subunits of respiratory chain complexes including new subunits of cytochrome bc1 complex
Author(s) -
Andrew E Maclean,
Hannah R. Bridges,
Mariana F. Silva,
Shuzhe Ding,
Jana Ovciarikova,
Judy Hirst,
Lilach Sheiner
Publication year - 2021
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1009301
Subject(s) - atp synthase , biology , protein subunit , atovaquone , respiratory chain , biochemistry , toxoplasma gondii , mitochondrion , mitochondrial disease , mitochondrial respiratory chain , microbiology and biotechnology , mitochondrial dna , genetics , enzyme , plasmodium falciparum , gene , malaria , antibody , immunology
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 assignment as complex III subunits. Our study highlights the divergent subunit composition of the apicomplexan mETC and F 1 F o -ATP synthase complexes and sets the stage for future structural and drug discovery studies.