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Mitochondrially targeted proximity biotinylation and proteomic analysis in Plasmodium falciparum
Journal article   Open access   Peer reviewed

Mitochondrially targeted proximity biotinylation and proteomic analysis in Plasmodium falciparum

Ian Lamb, Kelly Rios, Anurag Shukla, Avantika Ahiya, Joanne Morrisey, Joshua Mell, Scott Lindner, Michael Mather, Akhil Vaidya and Ashok B Vaidya
PloS one, v 17(8), pp e0273357-e0273357
01 Aug 2022
DOI: https://doi.org/10.1371/journal.pone.0273357
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1371/journal.pone.0273357View
Published, Version of Record (VoR)CC BY V4.0,  Open

Abstract

Antibodies Atovaquone Biology Biotin Biotinylation Cytochrome Ectopic expression Hsp60 protein Infections Labeling Localization Malaria Marking and tracking techniques Mass spectrometry Mass spectroscopy Mitochondria Mitochondrial DNA Parasite resistance Parasites Plasmids Plasmodium falciparum Proguanil Proteins Proteomics Tagging Therapeutic targets Vector-borne diseases
Despite ongoing efforts to control malaria infection, progress in lowering the number of deaths and infections appears to have stalled. The continued high incidence of malaria infection and mortality is in part due to emergence of parasites resistant to frontline antimalarials. This highlights the need for continued identification of novel protein drug targets. Mitochondrial functions in Plasmodium falciparum, the deadliest species of human malaria parasite, are targets of validated antimalarials including atovaquone and proguanil (Malarone). Thus, there has been great interest in identifying other essential mitochondrial proteins as candidates for novel drug targets. Garnering an increased understanding of the proteomic landscape inside the P. falciparum mitochondrion will also allow us to learn about the basic biology housed within this unique organelle. We employed a proximity biotinylation technique and mass spectrometry to identify novel P. falciparum proteins putatively targeted to the mitochondrion. We fused the leader sequence of a mitochondrially targeted chaperone, Hsp60, to the promiscuous biotin ligase TurboID. Through these experiments, we generated a list of 122 “putative mitochondrial” proteins. To verify whether these proteins were indeed mitochondrial, we chose five candidate proteins of interest for localization studies using ectopic expression and tagging of each full-length protein. This allowed us to localize four candidate proteins of unknown function to the mitochondrion, three of which have previously been assessed to be essential. We suggest that phenotypic characterization of these and other proteins from this list of 122 could be fruitful in understanding the basic mitochondrial biology of these parasites and aid antimalarial drug discovery efforts.

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10 citations in Web of Science
11 citations in Scopus

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Collaboration types
Domestic collaboration
Web of Science research areas
Biochemistry & Molecular Biology
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