title: A small mitochondrial protein present in myzozoans is essential for malaria transmission.
abstract: Myzozoans (which include dinoflagellates, chromerids and apicomplexans) display notable divergence from their ciliate sister group, including a reduced mitochondrial genome and divergent metabolic processes. The factors contributing to these divergent processes are still poorly understood and could serve as potential drug targets in disease-causing protists. Here, we report the identification and characterization of a small mitochondrial protein from the rodent-infecting apicomplexan parasite Plasmodium berghei that is essential for development in its mosquito host. Parasites lacking the gene mitochondrial protein ookinete developmental defect (mpodd) showed malformed parasites that were unable to transmit to mosquitoes. Knockout parasites displayed reduced mitochondrial mass without affecting organelle integrity, indicating no role of the protein in mitochondrial biogenesis or morphology maintenance but a likely role in mitochondrial import or metabolism. Using genetic complementation experiments, we identified a previously unrecognized Plasmodium falciparum homologue that can rescue the mpodd(-) phenotype, thereby showing that the gene is functionally conserved. As far as can be detected, mpodd is found in myzozoans, has homologues in the phylum Apicomplexa and appears to have arisen in free-living dinoflagellates. This suggests that the MPODD protein has a conserved mitochondrial role that is important for myzozoans. While previous studies identified a number of essential proteins which are generally highly conserved evolutionarily, our study identifies, for the first time, a non-canonical protein fulfilling a crucial function in the mitochondrion during parasite transmission.
authors.affiliation: Integrative Parasitology, Center for Infectious Diseases, Heidelberg University Medical School, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany dennis.klug@med.uni-heidelberg.de.
authors.forename: Dennis
authors.initials: D
authors.lastname: Klug
authors.affiliation: Integrative Parasitology, Center for Infectious Diseases, Heidelberg University Medical School, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany.
authors.forename: Gunnar R
authors.initials: GR
authors.lastname: Mair
authors.affiliation: Integrative Parasitology, Center for Infectious Diseases, Heidelberg University Medical School, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Frischknecht
authors.affiliation: Integrative Parasitology, Center for Infectious Diseases, Heidelberg University Medical School, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany ross.douglas@med.uni-heidelberg.de.
authors.forename: Ross G
authors.initials: RG
authors.lastname: Douglas
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D009033:Culicidae / Q000469:parasitology; D019143:Evolution, Molecular; D006801:Humans; D008018:Life Cycle Stages; D008288:Malaria / Q000469:parasitology / Q000635:transmission*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000378:metabolism*; D010271:Parasites / Q000254:growth & development / Q000378:metabolism; D010962:Plasmodium berghei / Q000254:growth & development / Q000378:metabolism*; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D015800:Protozoan Proteins
keywords: Plasmodium; alveolates; apicomplexa; mitochondrion; ookinete; transmission