Composition and stage dynamics of mitochondrial complexes in Plasmodium falciparum
Por:
Evers F., Cabrera-Orefice A., Elurbe D.M., Kea-te Lindert M., Boltryk S.D., Voss T.S., Huynen M.A., Brandt U., Kooij T.W.A.
Publicada:
1 ene 2021
Resumen:
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. © 2021, The Author(s).
Filiaciones:
Department of Medical Microbiology, Radboudumc Center for Infectious Diseases, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands
Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands
Centre for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands
Electron Microscopy Center, RTC Microscopy, Radboud Institute of Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands
Department of Cell Biology, Radboud Institute of Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland
University of Basel, Basel, Switzerland
Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany
All Open Access, Gold
|