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Rapid metabolic reprogramming mediated by the AMP-activated protein kinase during the lytic cycle of Toxoplasma gondii
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Rapid metabolic reprogramming mediated by the AMP-activated protein kinase during the lytic cycle of Toxoplasma gondii
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Journal Article
Rapid metabolic reprogramming mediated by the AMP-activated protein kinase during the lytic cycle of Toxoplasma gondii
2023
Overview
The ubiquitous pathogen
Toxoplasma gondii
has a complex lifestyle with different metabolic activities at different stages that are intimately linked to the parasitic environments. Here we identified the eukaryotic regulator of cellular homeostasis AMP-activated protein kinase (AMPK) in
Toxoplasma
and discovered its role in metabolic programming during parasite’s lytic cycle. The catalytic subunit AMPKα is quickly phosphorylated after the release of intracellular parasites to extracellular environments, driving energy-producing catabolism to power parasite motility and invasion into host cells. Once inside host cells, AMPKα phosphorylation is reduced to basal level to promote a balance between energy production and biomass synthesis, allowing robust parasite replication. AMPKγ depletion abolishes AMPKα phosphorylation and suppresses parasite growth, which can be partially rescued by overexpressing wildtype AMPKα but not the phosphorylation mutants. Thus, through the cyclic reprogramming by AMPK, the parasites’ metabolic needs at each stage are satisfied and the lytic cycle progresses robustly.
Efficient metabolic regulation is key for parasite growth. Here, the authors report that
Toxoplasma
alters its AMPK phosphorylation during the lytic cycle, which reprograms parasite’s metabolism to ensure metabolic needs at different stages are met.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
