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Free keywords:
Animals
Autophagy
Caco-2 Cells
Fatty Acids/*metabolism
Fibroblasts
Humans
Lipid Droplets/*metabolism
Mice
Mitochondria/*metabolism
*Mitochondrial Dynamics
Toxoplasma/*growth & development/*metabolism
Toxoplasmosis/immunology/*parasitology
*Toxoplasma gondii
*autophagy
*fusion
*lipid droplets
*lipid metabolism
*lipophagy
*mitochondria
*parasite
*beta-oxidation
Abstract:
How intracellular pathogens acquire essential non-diffusible host metabolites and whether the host cell counteracts the siphoning of these nutrients by its invaders are open questions. Here we show that host mitochondria fuse during infection by the intracellular parasite Toxoplasma gondii to limit its uptake of fatty acids (FAs). A combination of genetics and imaging of FA trafficking indicates that Toxoplasma infection triggers lipophagy, the autophagy of host lipid droplets (LDs), to secure cellular FAs essential for its proliferation. Indeed, Toxoplasma FA siphoning and growth are reduced in host cells genetically deficient for autophagy or triglyceride depots. Conversely, Toxoplasma FA uptake and proliferation are increased in host cells lacking mitochondrial fusion, required for efficient mitochondrial FA oxidation, or where mitochondrial FA oxidation is pharmacologically inhibited. Thus, mitochondrial fusion can be regarded as a cellular defense mechanism against intracellular parasites, by limiting Toxoplasma access to host nutrients liberated by lipophagy.
