Evers, Felix ORCID: 0000-0003-0527-9496, Cabrera-Orefice, Alfredo, Elurbe, Dei M., Kea-te Lindert, Mariska, Boltryk, Sylwia D., Voss, Till S., Huynen, Martijn A., Brandt, Ulrich
ORCID: 0000-0003-1869-6811 and Kooij, Taco W. A.
(2021).
Composition and stage dynamics of mitochondrial complexes in Plasmodium falciparum.
Nat. Commun., 12 (1).
BERLIN:
NATURE RESEARCH.
ISSN 2041-1723
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. 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.
Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||||||
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URN: | urn:nbn:de:hbz:38-587137 | ||||||||||||||||||||||||||||||||||||||||
DOI: | 10.1038/s41467-021-23919-x | ||||||||||||||||||||||||||||||||||||||||
Journal or Publication Title: | Nat. Commun. | ||||||||||||||||||||||||||||||||||||||||
Volume: | 12 | ||||||||||||||||||||||||||||||||||||||||
Number: | 1 | ||||||||||||||||||||||||||||||||||||||||
Date: | 2021 | ||||||||||||||||||||||||||||||||||||||||
Publisher: | NATURE RESEARCH | ||||||||||||||||||||||||||||||||||||||||
Place of Publication: | BERLIN | ||||||||||||||||||||||||||||||||||||||||
ISSN: | 2041-1723 | ||||||||||||||||||||||||||||||||||||||||
Language: | English | ||||||||||||||||||||||||||||||||||||||||
Faculty: | Unspecified | ||||||||||||||||||||||||||||||||||||||||
Divisions: | Unspecified | ||||||||||||||||||||||||||||||||||||||||
Subjects: | no entry | ||||||||||||||||||||||||||||||||||||||||
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URI: | http://kups.ub.uni-koeln.de/id/eprint/58713 |
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