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

Author

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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
    Key Laboratory of Preventive Medicine in Hubei Province
    Hubei Hongshan Laboratory)

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.

Suggested Citation

  • Yaqiong Li & Zhipeng Niu & Jichao Yang & Xuke Yang & Yukun Chen & Yingying Li & Xiaohan Liang & Jingwen Zhang & Fuqiang Fan & Ping Wu & Chao Peng & Bang Shen, 2023. "Rapid metabolic reprogramming mediated by the AMP-activated protein kinase during the lytic cycle of Toxoplasma gondii," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36084-0
    DOI: 10.1038/s41467-023-36084-0
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    1. Xuefang Guo & Nuo Ji & Qinghong Guo & Mengting Wang & Huiyu Du & Jiajia Pan & Lihua Xiao & Nishith Gupta & Yaoyu Feng & Ningbo Xia, 2024. "Metabolic plasticity, essentiality and therapeutic potential of ribose-5-phosphate synthesis in Toxoplasma gondii," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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