Felix Evers and Taco Kooij, theme Infectious diseases and global health, and colleagues showed in Nature Communications the composition and stage dynamics of mitochondrial complexes in Plasmodium falciparum.
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. In a collaborative effort involving four different teams from the Radboudumc and partners from Switzerland, 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.
Related news items
Grants for research on magnesium deficiency and malaria Vidis for Felix Hol and Jeroen de Baaij1 July 2022 Radboudumc researchers Jeroen de Baaij and Felix Hol both receive an NWO Vidi grant for their research, respectively on magnesium deficiency in type 2 diabetes and on malaria. read more
Field research on malaria vaccine offers unexpected surprise23 May 2022
Field research on the effectiveness of a malaria vaccine, came up with unexpected results for an international group of researchers including Benjamin Mordmüller of Radboudumc. The vaccine evokes a broader response against malaria proteins than there are in the vaccine.read more