Mitochondria restrict Toxoplasmagondii growth by limiting its fatty acids uptake Lena Pernas1,2, Camilla Bean1,2, John Boothroyd3 and Luca Scorrano1,2* 1Venetian Institute of Molecular Medicine, Via Orus 2, 35129 Padova, Italy; 2Department of Biology, University of Padova, Via U. Bassi 58B, 35121 Padova, Italy; 3Stanford University, Department of Microbiology and Immunology, Stanford, USA
How obligate 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 limit the uptake of fatty acids (FAs) by the human parasite Toxoplasma gondii by fusing during infection. A combination of genetics and imaging of FA trafficking between host organelles and parasites indicates that Toxoplasma infection triggers lipophagy, the autophagy of host lipid droplets (LDs), enabling the parasite to secure cellular FAs essential for its proliferation. The loss of host autophagy and triglyceride depots blunts parasite FA siphoning and growth. Conversely, loss of host mitochondrial fusion, required for efficient host FA oxidation, and inhibition of mitochondrial FA oxidation enhances Toxoplasma FA uptake and accelerates parasite proliferation. Thus, mitochondrial fusion appears to function as a cellular defense mechanism by restricting the access of an intracellular pathogen to host nutrients liberated by lipophagy.
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