IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-36084-0.html
   My bibliography  Save this article

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

Author

Listed:
  • 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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-36084-0
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-023-36084-0?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Alexander Lachmann & Denis Torre & Alexandra B. Keenan & Kathleen M. Jagodnik & Hoyjin J. Lee & Lily Wang & Moshe C. Silverstein & Avi Ma’ayan, 2018. "Massive mining of publicly available RNA-seq data from human and mouse," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    2. Liliana Mancio-Silva & Ksenija Slavic & Margarida T. Grilo Ruivo & Ana Rita Grosso & Katarzyna K. Modrzynska & Iset Medina Vera & Joana Sales-Dias & Ana Rita Gomes & Cameron Ross MacPherson & Pierre C, 2017. "Nutrient sensing modulates malaria parasite virulence," Nature, Nature, vol. 547(7662), pages 213-216, July.
    3. Jun Hee Lee & Hyongjong Koh & Myungjin Kim & Yongsung Kim & Soo Young Lee & Roger E. Karess & Sang-Hee Lee & Minho Shong & Jin-Man Kim & Jaeseob Kim & Jongkyeong Chung, 2007. "Energy-dependent regulation of cell structure by AMP-activated protein kinase," Nature, Nature, vol. 447(7147), pages 1017-1020, June.
    4. Danielle L. Schmitt & Stephanie D. Curtis & Anne C. Lyons & Jin-fan Zhang & Mingyuan Chen & Catherine Y. He & Sohum Mehta & Reuben J. Shaw & Jin Zhang, 2022. "Spatial regulation of AMPK signaling revealed by a sensitive kinase activity reporter," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    5. Chen-Song Zhang & Simon A. Hawley & Yue Zong & Mengqi Li & Zhichao Wang & Alexander Gray & Teng Ma & Jiwen Cui & Jin-Wei Feng & Mingjiang Zhu & Yu-Qing Wu & Terytty Yang Li & Zhiyun Ye & Shu-Yong Lin , 2017. "Fructose-1,6-bisphosphate and aldolase mediate glucose sensing by AMPK," Nature, Nature, vol. 548(7665), pages 112-116, August.
    6. Sebastian Lourido & Joel Shuman & Chao Zhang & Kevan M. Shokat & Raymond Hui & L. David Sibley, 2010. "Calcium-dependent protein kinase 1 is an essential regulator of exocytosis in Toxoplasma," Nature, Nature, vol. 465(7296), pages 359-362, May.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    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.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Yingfeng Tu & Qin Yang & Min Tang & Li Gao & Yuanhao Wang & Jiuqiang Wang & Zhe Liu & Xiaoyu Li & Lejiao Mao & Rui zhen Jia & Yuan Wang & Tie-shan Tang & Pinglong Xu & Yan Liu & Lunzhi Dai & Da Jia, 2024. "TBC1D23 mediates Golgi-specific LKB1 signaling," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    2. Jonathan P. Ling & Alexei M. Bygrave & Clayton P. Santiago & Rogger P. Carmen-Orozco & Vickie T. Trinh & Minzhong Yu & Yini Li & Ying Liu & Kyra D. Bowden & Leighton H. Duncan & Jeong Han & Kamil Tane, 2022. "Cell-specific regulation of gene expression using splicing-dependent frameshifting," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    3. Kenneth A. Wilson & Sudipta Bar & Eric B. Dammer & Enrique M. Carrera & Brian A. Hodge & Tyler A. U. Hilsabeck & Joanna Bons & George W. Brownridge & Jennifer N. Beck & Jacob Rose & Melia Granath-Pane, 2024. "OXR1 maintains the retromer to delay brain aging under dietary restriction," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    4. Hao Chen & Frederick J. King & Bin Zhou & Yu Wang & Carter J. Canedy & Joel Hayashi & Yang Zhong & Max W. Chang & Lars Pache & Julian L. Wong & Yong Jia & John Joslin & Tao Jiang & Christopher Benner , 2024. "Drug target prediction through deep learning functional representation of gene signatures," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    5. Yanling Zhang & Yafei Cao & Xia Wu & Zhenghui Chen & Bowen Chen & Anhui Wang & Yanshen Guo & Wei Chen & Ruolan Xue & Zihua Liu & Yuanpei Li & Tian Li & Ruiqin Cheng & Ning Zhou & Jing Li & Yuan Liu & , 2024. "Thermal proteome profiling reveals fructose-1,6-bisphosphate as a phosphate donor to activate phosphoglycerate mutase 1," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    6. Danielle L. Schmitt & Stephanie D. Curtis & Anne C. Lyons & Jin-fan Zhang & Mingyuan Chen & Catherine Y. He & Sohum Mehta & Reuben J. Shaw & Jin Zhang, 2022. "Spatial regulation of AMPK signaling revealed by a sensitive kinase activity reporter," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    7. Wei Lin & Abhishek Phatarphekar & Yanghao Zhong & Longwei Liu & Hyung-Bae Kwon & William H. Gerwick & Yingxiao Wang & Sohum Mehta & Jin Zhang, 2024. "Light-gated integrator for highlighting kinase activity in living cells," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    8. Javier Moral-Sanz & Sophronia A. Lewis & Sandy MacMillan & Marco Meloni & Heather McClafferty & Benoit Viollet & Marc Foretz & Jorge del-Pozo & A. Mark Evans, 2022. "AMPK deficiency in smooth muscles causes persistent pulmonary hypertension of the new-born and premature death," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    9. Milton Pividori & Sumei Lu & Binglan Li & Chun Su & Matthew E. Johnson & Wei-Qi Wei & Qiping Feng & Bahram Namjou & Krzysztof Kiryluk & Iftikhar J. Kullo & Yuan Luo & Blair D. Sullivan & Benjamin F. V, 2023. "Projecting genetic associations through gene expression patterns highlights disease etiology and drug mechanisms," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    10. Isabel Tundidor & Marta Seijo-Vila & Sandra Blasco-Benito & María Rubert-Hernández & Sandra Adámez & Clara Andradas & Sara Manzano & Isabel Álvarez-López & Cristina Sarasqueta & María Villa-Morales & , 2023. "Identification of fatty acid amide hydrolase as a metastasis suppressor in breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    11. Lucas A. Mavromatis & Daniel B. Rosoff & Andrew S. Bell & Jeesun Jung & Josephin Wagner & Falk W. Lohoff, 2023. "Multi-omic underpinnings of epigenetic aging and human longevity," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    12. Daewon Lee & Eunju Yoon & Su Jin Ham & Kunwoo Lee & Hansaem Jang & Daihn Woo & Da Hyun Lee & Sehyeon Kim & Sekyu Choi & Jongkyeong Chung, 2024. "Diabetic sensory neuropathy and insulin resistance are induced by loss of UCHL1 in Drosophila," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    13. Jaishree Tripathi & Lei Zhu & Sourav Nayak & Michal Stoklasa & Zbynek Bozdech, 2022. "Stochastic expression of invasion genes in Plasmodium falciparum schizonts," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    14. Juliane Tschuck & Lea Theilacker & Ina Rothenaigner & Stefanie A. I. Weiß & Banu Akdogan & Van Thanh Lam & Constanze Müller & Roman Graf & Stefanie Brandner & Christian Pütz & Tamara Rieder & Philippe, 2023. "Farnesoid X receptor activation by bile acids suppresses lipid peroxidation and ferroptosis," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    15. Nikolai Schleussner & Pierre Cauchy & Vedran Franke & Maciej Giefing & Oriol Fornes & Naveen Vankadari & Salam A. Assi & Mariantonia Costanza & Marc A. Weniger & Altuna Akalin & Ioannis Anagnostopoulo, 2023. "Transcriptional reprogramming by mutated IRF4 in lymphoma," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    16. Florent Peglion & Lavinia Capuana & Isabelle Perfettini & Laurent Boucontet & Ben Braithwaite & Emma Colucci-Guyon & Emie Quissac & Karin Forsberg-Nilsson & Flora Llense & Sandrine Etienne-Manneville, 2022. "PTEN inhibits AMPK to control collective migration," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    17. Luigi Mazzeo & Soumitra Ghosh & Emery Di Cicco & Jovan Isma & Daniele Tavernari & Anastasia Samarkina & Paola Ostano & Markus K. Youssef & Christian Simon & G. Paolo Dotto, 2024. "ANKRD1 is a mesenchymal-specific driver of cancer-associated fibroblast activation bridging androgen receptor loss to AP-1 activation," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    18. Xiaochu Tong & Ning Qu & Xiangtai Kong & Shengkun Ni & Jingyi Zhou & Kun Wang & Lehan Zhang & Yiming Wen & Jiangshan Shi & Sulin Zhang & Xutong Li & Mingyue Zheng, 2024. "Deep representation learning of chemical-induced transcriptional profile for phenotype-based drug discovery," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    19. Elizabeth Haythorne & Matthew Lloyd & John Walsby-Tickle & Andrei I. Tarasov & Jonas Sandbrink & Idoia Portillo & Raul Terron Exposito & Gregor Sachse & Malgorzata Cyranka & Maria Rohm & Patrik Rorsma, 2022. "Altered glycolysis triggers impaired mitochondrial metabolism and mTORC1 activation in diabetic β-cells," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    20. Zhenzhen Zi & Zhuzhen Zhang & Qiang Feng & Chiho Kim & Xu-Dong Wang & Philipp E. Scherer & Jinming Gao & Beth Levine & Yonghao Yu, 2022. "Quantitative phosphoproteomic analyses identify STK11IP as a lysosome-specific substrate of mTORC1 that regulates lysosomal acidification," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36084-0. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.