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ATAD3 megadalton complex in Plasmodium falciparum is essential for mitochondrial and cellular viability
Journal article   Open access   Peer reviewed

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

Ijeoma C Okoye, Ian M Lamb, Yee-Wai Cheung, Joanne M Morrisey, Manish Sharma, Rajat Kumar, Swati Dass, Anurag Shukla, River S Rell, Michael W Mather, …
PLoS pathogens, v 22(6), e1014317
01 Jun 2026
DOI: https://doi.org/10.1371/journal.ppat.1014317
PMID: 42234699
url
https://doi.org/10.1371/journal.ppat.1014317View
Published, Version of Record (VoR) Open

Abstract

ATPases Associated with Diverse Cellular Activities Cell Survival Humans Malaria, Falciparum - metabolism Malaria, Falciparum - parasitology Membrane Potential, Mitochondrial Membrane Proteins - genetics Membrane Proteins - metabolism Mitochondria - genetics Mitochondria - metabolism Mitochondrial Proteins - genetics Mitochondrial Proteins - metabolism Plasmodium falciparum - genetics Plasmodium falciparum - metabolism Protozoan Proteins - genetics Protozoan Proteins - metabolism
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.

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