Universität zu Köln

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

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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
Creators:	Creators Email ORCID ORCID Put Code Evers, Felix UNSPECIFIED orcid.org/0000-0003-0527-9496 UNSPECIFIED Cabrera-Orefice, Alfredo UNSPECIFIED UNSPECIFIED UNSPECIFIED Elurbe, Dei M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kea-te Lindert, Mariska UNSPECIFIED UNSPECIFIED UNSPECIFIED Boltryk, Sylwia D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Voss, Till S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Huynen, Martijn A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Brandt, Ulrich UNSPECIFIED orcid.org/0000-0003-1869-6811 UNSPECIFIED Kooij, Taco W. A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
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
Uncontrolled Keywords:	Keywords Language PROTEIN-INTERACTION NETWORK; ATP SYNTHASE; ERYTHROCYTIC STAGES; ELECTRON-TRANSPORT; RIBOSOMAL-RNA; MALARIA; CRISTAE; PURIFICATION; APICOMPLEXA; EXPRESSION Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/58713