Journal
EMBO REPORTS
Volume 21, Issue 3, Pages -Publisher
WILEY
DOI: 10.15252/embr.201947832
Keywords
malaria; oocyst; ookinete; sporozoite; transhydrogenase; transmission
Categories
Funding
- UK Medical Research Council (MRC) [MR/P021611]
- UK Department for International Development (DFID) [MR/P021611]
- Wellcome Trust [088449]
- UK Biotechnology and Biological Sciences Research Council [BB/M001598]
- BBSRC [BB/M001598/1] Funding Source: UKRI
- MRC [MR/P021611/1] Funding Source: UKRI
Ask authors/readers for more resources
Nicotinamide adenine dinucleotide (NAD) and its phosphorylated form (NADP) are vital for cell function in all organisms and form cofactors to a host of enzymes in catabolic and anabolic processes. NAD(P) transhydrogenases (NTHs) catalyse hydride ion transfer between NAD(H) and NADP(H). Membrane-bound NTH isoforms reside in the cytoplasmic membrane of bacteria, and the inner membrane of mitochondria in metazoans, where they generate NADPH. Here, we show that malaria parasites encode a single membrane-bound NTH that localises to the crystalloid, an organelle required for sporozoite transmission from mosquitos to vertebrates. We demonstrate that NTH has an essential structural role in crystalloid biogenesis, whilst its enzymatic activity is required for sporozoite development. This pinpoints an essential function in sporogony to the activity of a single crystalloid protein. Its additional presence in the apicoplast of sporozoites identifies NTH as a likely supplier of NADPH for this organelle during liver infection. Our findings reveal that Plasmodium species have co-opted NTH to a variety of non-mitochondrial organelles to provide a critical source of NADPH reducing power.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available