A prioritized and validated resource of mitochondrial proteins in Plasmodium identifies leads to unique biology

Abstract

Plasmodium species have a single mitochondrion that is essential for their survival and has been successfully targeted by anti-malarial drugs. Most 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 expression profiles, orthology to mitochondrial proteins from other species, co-evolutionary 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 datasets using Bayesian statistics into a predictive score per protein for mitochondrial localization. At a corrected false discovery rate of 25%, we identified 295 proteins with a sensitivity of 65% and a specificity of 98%. 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 co-localization 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.

Transcriptional changes in Plasmodium falciparum upon conditional knock down of mitochondrial ribosomal proteins RSM22 and L23

“…Although the complete mito-proteome of P. falciparum remains to be established, recent investigations of organellar proteins based on fractionation and bioinformatic approaches have generated lists of potential nuclearly-encoded proteins that are likely translocated to the parasite mitochondrion. We selected 475 proteins as a putative (unavoidably incomplete) mito-proteome based on manual annotation (41), Plasmodium orthologues of Toxoplasma mito-proteome (42,43) and selected proteins listed in PlasmoMitoCarta (17). This curated list along with 42 mtDNA encoded transcripts (Table S4) is denoted “mitochondria related transcripts” herein.…”

“…Currently, 43 putative MRPs in Plasmodium falciparum (Pf) have been annotated based on their sequence similarity with known MRPs of bacterial and mitochondrial origin (www.PlasmoDB.org). However, the species-specific Plasmodium MRPs remain entirely unknown (16,17). We have previously studied four annotated MRPs in P. falciparum , including PfMRPL13, PfMRPS12, PfMRPS17, and PfMRPS 18 (18,19).…”