Cell Microbiol. 2011 Dec 30. doi: 10.1111/j.1462-5822.2011.01745.x. [Epub ahead of print]
Autophagy is a cell death mechanism in Toxoplasma gondii.
Ghosh D, Walton JL, Roepe PD, Sinai AP.
Department of Microbiology, Immunology and Molecular Genetics; University of Kentucky College of Medicine, Lexington KY 40536, USA. Departments of Chemistry, Biochemistry and Cellular and Molecular Biology, Georgetown University, Washington DC. 20057, USA.
Nutrient sensing and the capacity to respond to starvation is tightly regulated as a means of cell survival. Among the features of the starvation response are induction of both translational repression and autophagy. Despite the fact that intracellular parasite like Toxoplasma gondii within a host cell predicted to be nutrient rich, they encode genes involved both in translational repression and autophagy. We therefore examined the consequence of starvation, a classic trigger of autophagy, on intracellular parasites. As expected, starvation results in the activation of the translational repression system as evidenced by elevation of phosphorylated TgIF2α (TgIF2α-P). Surprisingly, we also observe a rapid and selective fragmentation of the single parasite mitochondrion that leads irreversibly to parasite death. This profound effect was dependent primarily on the limitation of amino acids and involved signaling by the parasite TOR homolog. Notably, the effective blockade of mitochondrial fragmentation by the autophagy inhibitor 3-methyl adenine (3-MA) suggests an autophagic mechanism. In the absence of a documented apoptotic cascade in T. gondii, the data suggest that autophagy is the primary mechanism of programmed cell death in T. gondii and potentially other related parasites.
© 2011 Blackwell Publishing Ltd.
PMID: 22212386 [PubMed - as supplied by publisher]