A Prioritized and Validated Resource of Mitochondrial Proteins in Plasmodium Identifies Unique Biology
van Esveld, Selma L; Meerstein-Kessel, Lisette; Boshoven, Cas; Baaij, Jochem F; Barylyuk, Konstantin; Coolen, Jordy P M; van Strien, Joeri; Duim, Ronald A J; Dutilh, Bas E; Garza, Daniel R; Letterie, Marijn; Proellochs, Nicholas I; de Ridder, Michelle N; Venkatasubramanian, Prashanna Balaji; de Vries, Laura E; Waller, Ross F; Kooij, Taco W A; Huynen, Martijn A
(2021) mSphere, volume 6, issue 5, pp. 1 - 17
(Article)
Abstract
Plasmodium species have a single mitochondrion that is essential for their survival and has been successfully targeted by antimalarial drugs. Most mitochondrial proteins are imported into this organelle, and our picture of the Plasmodium mitochondrial proteome remains incomplete. Many data sources contain information about mitochondrial localization, including proteome and gene
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expression profiles, orthology to mitochondrial proteins from other species, coevolutionary relationships, and amino acid sequences, each with different coverage and reliability. To obtain a comprehensive, prioritized list of Plasmodium falciparum mitochondrial proteins, we rigorously analyzed and integrated eight data sets using Bayesian statistics into a predictive score per protein for mitochondrial localization. At a corrected false discovery rate of 25%, we identified 445 proteins with a sensitivity of 87% and a specificity of 97%. They include proteins that have not been identified as mitochondrial in other eukaryotes but have characterized homologs in bacteria that are involved in metabolism or translation. Mitochondrial localization of seven Plasmodium berghei orthologs was confirmed by epitope labeling and colocalization with a mitochondrial marker protein. One of these belongs to a newly identified apicomplexan mitochondrial protein family that in P. falciparum has four members. With the experimentally validated mitochondrial proteins and the complete ranked P. falciparum proteome, which we have named PlasmoMitoCarta, we present a resource to study unique proteins of Plasmodium mitochondria.
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Keywords: Bayesian data integration, Mitochondria, Plasmodium, Microbiology, Molecular Biology
ISSN: 2379-5042
Publisher: American Society for Microbiology
Note: Funding Information: S.L.V.E., L.M., and C.B. were supported by Ph.D. fellowships from the Radboud Institute for Molecular Life Sciences, Radboudumc (Radboudumc JO ronde 2014 and #19-015a). N.I.P. was supported by a Marie-Sklodowska Curie grant (790085), and T.W.A.K. and L.E.D.V. by the Netherlands Organisation for Scientific Research (NWO-VIDI 864.13.009). B.E.D. was supported by the Netherlands Organization for Scientific Research (NWO) Vidi grant 864.14.004 and European Research Council (ERC) Consolidator grant 865694: DiversiPHI. K.B. was supported by a Leverhulme Trust and Isaac Newton Trust Fellowship (ECF-2015-562), and R.F.W. by the Wellcome Trust (214298/Z/18/Z). J.V.S. was funded by the by a grant from the Dutch Organisation for Health Research and Development (ZON-MW TOP grant number 91217009). We declare no competing interests. Publisher Copyright: © 2021 American Society for Microbiology. All rights reserved.
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