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Composition and stage dynamics of mitochondrial complexes in Plasmodium falciparum
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Composition and stage dynamics of mitochondrial complexes in Plasmodium falciparum
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Journal Article
Composition and stage dynamics of mitochondrial complexes in Plasmodium falciparum
2021
Overview
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.
Applying complexome profiling, Evers et al. unravel the composition of mitochondrial oxidative phosphorylation complexes in
P. falciparum
asexual and sexual blood stages. Abundance of these complexes differs between both stages, supporting the hypothesis that a mitochondrial metabolic switch is central to gametocyte development and functioning.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 82/29
/ 82/58
/ Blood
/ Chains
/ Cristae
/ Electron Transport Chain Complex Proteins - metabolism
/ Electron Transport Chain Complex Proteins - ultrastructure
/ Humanities and Social Sciences
/ Malaria
/ Mitochondria - ultrastructure
/ Mitochondrial Proteins - metabolism
/ Mitochondrial Proteins - ultrastructure
/ Multiprotein Complexes - metabolism
/ Multiprotein Complexes - ultrastructure
/ Plasmodium falciparum - growth & development
/ Plasmodium falciparum - metabolism
/ Plasmodium falciparum - ultrastructure
/ Protozoan Proteins - metabolism
/ Protozoan Proteins - ultrastructure
/ Science
