ATAD3 megadalton complex in Plasmodium falciparum is essential for mitochondrial and cellular viability

Malaria remains an urgent threat to global health as the mortality and infection rates keep rising annually and our frontline antimalarials are becoming less effective due to the emergence and spread of resistance-conferring mutations. Although the mitochondrion of P. falciparum parasites is a validated drug target, there remain many uncharacterized mitochondrial proteins. The goal of this study was to investigate the essentiality and functions of a recently identified mitochondrial protein - PF3D7_0707400. Our results show that PF3D7_0707400 is an ATAD3A homolog that is essential to parasite survival and is present in a megadalton complex that is critical for multiple mitochondrial processes such as mitochondrial RNA stability, membrane potential, ultrastructure, and protein import. ATAD3A has been previously studied in multicellular eukaryotes and has been implicated in several childhood mitochondrial diseases, with suggested functions in mitochondrial nucleoid stabilization, mitochondrial RNA translation, and mitochondrial inner membrane integrity. This study is the first characterization, to our knowledge, of ATAD3A in unicellular organisms. Our findings here expand our knowledge on apicomplexan mitochondrial biology and our arsenal of potential antimalarial drug targets.