The Toxoplasma gondii mitochondrial transporter ABCB7L is essential for the biogenesis of cytosolic and nuclear iron-sulfur cluster proteins and cytosolic translation

Iron-sulfur (Fe-S) clusters are ubiquitous inorganic cofactors required for numerous essential cellular pathways. Since they cannot be scavenged from the environment, Fe-S clusters are synthesized de novo in cellular compartments such as the apicoplast, mitochondrion, and cytosol. The cytosolic Fe-S cluster biosynthesis pathway relies on the transport of an intermediate from the mitochondrial pathway. An ATP-binding cassette (ABC) transporter called ABCB7 is responsible for this role in numerous commonly studied organisms, but its role in the medically important apicomplexan parasites has not yet been studied. Here we identify and characterize a Toxoplasma gondii ABCB7 homolog, which we name ABCB7-like (ABCB7L). Genetic depletion shows that it is essential for parasite growth and that its disruption triggers partial stage conversion. Characterization of the knock-down line highlights a defect in the biogenesis of cytosolic and nuclear Fe-S proteins leading to defects in protein translation and other pathways including DNA and RNA replication and metabolism. Our work provides support for a broad conservation of the connection between mitochondrial and cytosolic pathways in Fe-S cluster biosynthesis and reveals its importance for parasite survival.