Investigating the response to iron deprivation in Toxoplasma

Iron is essential for almost all life due to its role as a cofactor in numerous biological processes. Excess iron is however toxic, meaning regulation of cellular iron abundance is critical. For Toxoplasma gondii iron must be obtained from host cells, however its host cell promiscuity means it must contend with diverse and dynamic levels of accessible iron. To investigate how Toxoplasma regulate and respond to changing iron availability, we used quantitative proteomics to determine the impact of iron deprivation on the Toxoplasma proteome. We analysed changes to 4742 proteins from Toxoplasma tachyzoites and found that 1373 proteins had significant changes in their abundance. Of these significant changes, 835 proteins were downregulated, suggesting a general decrease in protein abundance in response to iron deprivation. Low iron predictably induced downregulation of proteins associated with DNA replication, supporting previous observations of reduced growth under these conditions. Iron deprived parasites also exhibited a downregulation of translation machinery and an accompanying reduction to translation measured by puromycin incorporation. Despite this reduction to translation, proteins related to glycolysis are upregulated in these iron deprived parasites. Metabolic analysis determined that these parasites also exhibit a reduction in mitochondrial oxygen consumption. These data highlight the importance of iron to diverse processes and indicate that while downregulating protein synthesis Toxoplasma also rewire their metabolism in response to iron deprivation.