Characterization of the ATG8-conjugation system in 2 Plasmodium species with special focus on the liver stage: Possible linkage between the apicoplastic and autophagic systems?

Bamini Jayabalasingham, Christiane Voss, Karen Ehrenman, Julia D. Romano, Maria E. Smith, David A. Fidock, Juergen Bosch, Isabelle Coppens

Research output: Contribution to journalArticle

Abstract

Plasmodium parasites successfully colonize different habitats within mammals and mosquitoes, and adaptation to various environments is accompanied by changes in their organelle composition and size. Previously, we observed that during hepatocyte infection, Plasmodium discards organelles involved in invasion and expands those implicated in biosynthetic pathways. We hypothesized that this process is regulated by autophagy. Plasmodium spp. possess a rudimentary set of known autophagy-related proteins that includes the ortholog of yeast Atg8. In this study, we analyzed the activity of the ATG8-conjugation pathway over the course of the lifecycle of Plasmodium falciparum and during the liver stage of Plasmodium berghei. We engineered a transgenic P. falciparum strain expressing mCherry-PfATG8. These transgenic parasites expressed mCherry-PfATG8 in human hepatocytes and erythrocytes, and in the midgut and salivary glands of Anopheles mosquitoes. In all observed stages, mCherry-PfATG8 was localized to tubular structures. Our EM and colocalization studies done in P. berghei showed the association of PbATG8 on the limiting membranes of the endosymbiont-derived plastid-like organelle known as the apicoplast. Interestingly, during parasite replication in hepatocytes, the association of PbATG8 with the apicoplast increases as this organelle expands in size. PbATG3, PbATG7 and PbATG8 are cotranscribed in all parasitic stages. Molecular analysis of PbATG8 and PbATG3 revealed a novel mechanism of interaction compared with that observed for other orthologs. This is further supported by the inability of Plasmodium ATG8 to functionally complement atg8Δ yeast or localize to autophagosomes in starved mammalian cells. Altogether, these data suggests a unique role for the ATG8-conjugation system in Plasmodium parasites.

Original languageEnglish (US)
Pages (from-to)269-284
Number of pages16
JournalAutophagy
Volume10
Issue number2
DOIs
StatePublished - Feb 2014

Keywords

  • ATG8
  • Apicoplast
  • Autophagy-related genes
  • Cellular differentiation
  • Malaria
  • Plasmodium liver forms

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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