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Plasmodium falciparum OTU‐like cysteine protease (PfOTU) is essential for apicoplast homeostasis and associates with noncanonical role of Atg8
Authors:Gaurav Datta  Mohammad E Hossain  Mohd Asad  Sumit Rathore  Asif Mohmmed
Institution:1. International Centre for Genetic Engineering and Biotechnology, New Delhi, India;2. Department of Biotechnology, All India Institute of Medical Sciences, New Delhi, India
Abstract:The metabolic pathways associated with the mitochondrion and the apicoplast in Plasmodium, 2 parasite organelles of prokaryotic origin, are considered as suitable drug targets. In the present study, we have identified functional role of a novel ovarian tumour unit (OTU) domain‐containing cysteine protease of Plasmodium falciparum (PfOTU). A C‐terminal regulatable fluorescent affinity tag on native protein was utilised for its localization and functional characterization. Detailed studies showed vesicular localization of PfOTU and its association with the apicoplast. Degradation‐tag mediated knockdown of PfOTU resulted in abnormal apicoplast development and blocked development of parasites beyond early‐schizont stages in subsequent cell cycle; downregulation of PfOTU hindered apicoplast protein import. Further, the isoprenoid precursor‐mediated parasite growth‐rescue experiments confirmed that PfOTU knockdown specifically effect development of functional apicoplast. We also provide evidence for a possible biological function of PfOTU in membrane deconjugation of Atg8, which may be linked with the apicoplast protein import. Overall, our results show that the PfOTU is involved in apicoplast homeostasis and associates with the noncanonical function of Atg8 in maintenance of parasite apicoplast.
Keywords:apicoplast  autophagy‐linked protein Atg8  malaria  OTU‐like protease  Plasmodium  regulatable fluorescent affinity tag
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