Authors

B Preece¹;  ¹ University of Glasgow , UK

Discussion

The apicomplexan mitochondrial electron transport chain (mETC) and ATP synthase are crucial for parasite energy metabolism and survival. They are highly divergent from the mammalian mETC, with parasite-specific subunits that could prove to be valuable drug targets for anti-parasitic treatment. This project focuses on two of these subunits: the mETC complex IV subunit ApiCox10 and the ATP synthase subunit ATPTG11. Both subunits have a vital role in the formation of higher-order assemblies: Apicox10 is required to form associations between mETC complexes, “Supercomplexes”. ATPTG11 is required for ATP synthase hexamerisation in Toxoplasma gondii. Higher complex formation may enhance metabolic efficiency by improving electron diffusion between complexes, protection from reactive oxygen species or provide relevant structural features to the mitochondrial membrane. For example, T. gondii’s ATP synthase’s hexameric structure shapes the cristae of the mitochondria, enhancing ATP synthase metabolism. Previous studies have shown that knockout of ApiCox10 prevents the formation of the III-IV supercomplex, resulting in minor growth defects in tachyzoites in vitro, and that a knockout of ATPTG11, which results in ATP synthase dimers rather than hexamers, shows similar results. However, the extent of the loss of metabolic activity in ATPTG11- KO culture, the effects on bradyzoite formation and health and parasite survival in vitro are yet to be explored and will be the focus of this project. This poster summarises the focus of my first year of this project: The analysis and characterisation of the effects of the removal of higher-order assemblies from T. gondii’s mETC on parasite fitness in vitro.