Composition and stage dynamics of mitochondrial complexes in Plasmodium falciparum

Felix Evers, Alfredo Cabrera-Orefice, Dei M. Elurbe, Mariska Kea-te Lindert, Sylwia D. Boltryk, Till S. Voss, Martijn A. Huynen, Ulrich Brandt and Taco W. A. Kooij ()
Additional contact information
Felix Evers: Radboudumc Center for Infectious Diseases, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center
Alfredo Cabrera-Orefice: Radboud University Medical Center
Dei M. Elurbe: Radboud University Medical Center
Mariska Kea-te Lindert: Radboud University Medical Center
Sylwia D. Boltryk: Swiss Tropical and Public Health Institute
Till S. Voss: Swiss Tropical and Public Health Institute
Martijn A. Huynen: Radboud University Medical Center
Ulrich Brandt: Radboud University Medical Center
Taco W. A. Kooij: Radboudumc Center for Infectious Diseases, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: Abstract Our current understanding of mitochondrial functioning is largely restricted to traditional model organisms, which only represent a fraction of eukaryotic diversity. The unusual mitochondrion of malaria parasites is a validated drug target but remains poorly understood. Here, we apply complexome profiling to map the inventory of protein complexes across the pathogenic asexual blood stages and the transmissible gametocyte stages of Plasmodium falciparum. We identify remarkably divergent composition and clade-specific additions of all respiratory chain complexes. Furthermore, we show that respiratory chain complex components and linked metabolic pathways are up to 40-fold more prevalent in gametocytes, while glycolytic enzymes are substantially reduced. Underlining this functional switch, we find that cristae are exclusively present in gametocytes. Leveraging these divergent properties and stage dynamics for drug development presents an attractive opportunity to discover novel classes of antimalarials and increase our repertoire of gametocytocidal drugs.

Date: 2021
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DOI: 10.1038/s41467-021-23919-x

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