title: Features of autophagic cell death in Plasmodium liver-stage parasites.
abstract: Analyzing molecular determinants of Plasmodium parasite cell death is a promising approach for exploring new avenues in the fight against malaria. Three major forms of cell death (apoptosis, necrosis and autophagic cell death) have been described in multicellular organisms but which cell death processes exist in protozoa is still a matter of debate. Here we suggest that all three types of cell death occur in Plasmodium liver-stage parasites. Whereas typical molecular markers for apoptosis and necrosis have not been found in the genome of Plasmodium parasites, we identified genes coding for putative autophagy-marker proteins and thus concentrated on autophagic cell death. We characterized the Plasmodium berghei homolog of the prominent autophagy marker protein Atg8/LC3 and found that it localized to the apicoplast. A relocalization of PbAtg8 to autophagosome-like vesicles or vacuoles that appear in dying parasites was not, however, observed. This strongly suggests that the function of this protein in liver-stage parasites is restricted to apicoplast biology.
authors: Institute of Cell Biology, University of Bern, Bern, Switzerland.
authors: Nina
authors: N
authors: Eickel
authors: Gesine
authors: G
authors: Kaiser
authors: Monica
authors: M
authors: Prado
authors: Paul-Christian
authors: PC
authors: Burda
authors: Matthias
authors: M
authors: Roelli
authors: Rebecca R
authors: RR
authors: Stanway
authors: Volker T
authors: VT
authors: Heussler
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001343:Autophagy; D017124:Conserved Sequence; D030562:Databases, Protein; D019143:Evolution, Molecular; D055786:Gene Knockout Techniques; D005816:Genetic Complementation Test; D049452:Green Fluorescent Proteins / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D008018:Life Cycle Stages; D050356:Lipid Metabolism; D008099:Liver / Q000469:parasitology*; D051379:Mice; D008969:Molecular Sequence Data; D010271:Parasites / Q000166:cytology* / Q000254:growth & development* / Q000648:ultrastructure; D010588:Phagosomes / Q000378:metabolism / Q000648:ultrastructure; D010962:Plasmodium berghei / Q000166:cytology* / Q000254:growth & development* / Q000648:ultrastructure; D021381:Protein Transport; D015800:Protozoan Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D052939:Schizonts / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D017386:Sequence Homology, Amino Acid; D014617:Vacuoles / Q000378:metabolism
chemical_list: D015800:Protozoan Proteins; D049452:Green Fluorescent Proteins
keywords: Atg3; Atg7; Atg8; Plasmodium liver-stage; apicoplast; autophagy-like cell death; malaria; membrane expansion; organelle growth; parasite death
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