Rapid metabolic reprogramming mediated by the AMP-activated protein kinase during the lytic cycle of Toxoplasma gondii

Yaqiong Li, Zhipeng Niu, Jichao Yang, Xuke Yang, Yukun Chen, Yingying Li, Xiaohan Liang, Jingwen Zhang, Fuqiang Fan, Ping Wu, Chao Peng and Bang Shen ()
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Yaqiong Li: Huazhong Agricultural University
Zhipeng Niu: Huazhong Agricultural University
Jichao Yang: Huazhong Agricultural University
Xuke Yang: Huazhong Agricultural University
Yukun Chen: Huazhong Agricultural University
Yingying Li: Huazhong Agricultural University
Xiaohan Liang: Huazhong Agricultural University
Jingwen Zhang: Huazhong Agricultural University
Fuqiang Fan: Huazhong Agricultural University
Ping Wu: Chinese Academy of Science
Chao Peng: Chinese Academy of Science
Bang Shen: Huazhong Agricultural University

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-023-36084-0

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