IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-37148-x.html
   My bibliography  Save this article

A mycobacterial effector promotes ferroptosis-dependent pathogenicity and dissemination

Author

Listed:
  • Lihua Qiang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Yong Zhang

    (Chinese Academy of Sciences)

  • Zehui Lei

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Zhe Lu

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Shasha Tan

    (Chinese Academy of Sciences)

  • Pupu Ge

    (Chinese Academy of Sciences)

  • Qiyao Chai

    (Chinese Academy of Sciences)

  • Mengyuan Zhao

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Xinwen Zhang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Bingxi Li

    (Chinese Academy of Sciences)

  • Yu Pang

    (Capital Medical University)

  • Lingqiang Zhang

    (Beijing Institute of Lifeomics)

  • Cui Hua Liu

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Jing Wang

    (Chinese Academy of Sciences)

Abstract

Ferroptosis is a lipid peroxidation-driven and iron-dependent programmed cell death involved in multiple physical processes and various diseases. Emerging evidence suggests that several pathogens manipulate ferroptosis for their pathogenicity and dissemination, but the underlying molecular mechanisms remain elusive. Here, we identify that protein tyrosine phosphatase A (PtpA), an effector secreted by tuberculosis (TB)-causing pathogen Mycobacterium tuberculosis (Mtb), triggers ferroptosis to promote Mtb pathogenicity and dissemination. Mechanistically, PtpA, through its Cys11 site, interacts with host RanGDP to enter host cell nucleus. Then, the nuclear PtpA enhances asymmetric dimethylation of histone H3 arginine 2 (H3R2me2a) via targeting protein arginine methyltransferase 6 (PRMT6), thus inhibiting glutathione peroxidase 4 (GPX4) expression, eventually inducing ferroptosis to promote Mtb pathogenicity and dissemination. Taken together, our findings provide insights into molecular mechanisms of pathogen-induced ferroptosis, indicating a potential TB treatment via blocking Mtb PtpA-host PRMT6 interface to target GPX4-dependent ferroptosis.

Suggested Citation

  • Lihua Qiang & Yong Zhang & Zehui Lei & Zhe Lu & Shasha Tan & Pupu Ge & Qiyao Chai & Mengyuan Zhao & Xinwen Zhang & Bingxi Li & Yu Pang & Lingqiang Zhang & Cui Hua Liu & Jing Wang, 2023. "A mycobacterial effector promotes ferroptosis-dependent pathogenicity and dissemination," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37148-x
    DOI: 10.1038/s41467-023-37148-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-37148-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-37148-x?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. Jing Wang & Pupu Ge & Lihua Qiang & Feng Tian & Dongdong Zhao & Qiyao Chai & Mingzhao Zhu & Rongbin Zhou & Guangxun Meng & Yoichiro Iwakura & George Fu Gao & Cui Hua Liu, 2017. "The mycobacterial phosphatase PtpA regulates the expression of host genes and promotes cell proliferation," Nature Communications, Nature, vol. 8(1), pages 1-16, December.
    2. Imtiyaz Yaseen & Prabhjot Kaur & Vinay Kumar Nandicoori & Sanjeev Khosla, 2015. "Mycobacteria modulate host epigenetic machinery by Rv1988 methylation of a non-tail arginine of histone H3," Nature Communications, Nature, vol. 6(1), pages 1-13, December.
    3. Zhennan Shi & Nathchar Naowarojna & Zijian Pan & Yilong Zou, 2021. "Multifaceted mechanisms mediating cystine starvation-induced ferroptosis," Nature Communications, Nature, vol. 12(1), pages 1-4, December.
    4. Ernesto Guccione & Christian Bassi & Fabio Casadio & Francesca Martinato & Matteo Cesaroni & Henning Schuchlautz & Bernhard Lüscher & Bruno Amati, 2007. "Methylation of histone H3R2 by PRMT6 and H3K4 by an MLL complex are mutually exclusive," Nature, Nature, vol. 449(7164), pages 933-937, October.
    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. Boyi Gan, 2023. "Ferroptosis hijacking by Mycobacterium tuberculosis," Nature Communications, Nature, vol. 14(1), pages 1-3, 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. Ramachandran Prakasam & Angela Bonadiman & Roberta Andreotti & Emanuela Zuccaro & Davide Dalfovo & Caterina Marchioretti & Debasmita Tripathy & Gianluca Petris & Eric N. Anderson & Alice Migazzi & Lau, 2023. "LSD1/PRMT6-targeting gene therapy to attenuate androgen receptor toxic gain-of-function ameliorates spinobulbar muscular atrophy phenotypes in flies and mice," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    2. Ying Xue & Fujia Lu & Zhenzhen Chang & Jing Li & Yuan Gao & Jie Zhou & Ying Luo & Yongfeng Lai & Siyuan Cao & Xiaoxiao Li & Yuhan Zhou & Yan Li & Zheng Tan & Xiang Cheng & Xiong Li & Jing Chen & Weimi, 2023. "Intermittent dietary methionine deprivation facilitates tumoral ferroptosis and synergizes with checkpoint blockade," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    3. Benjamin A. Nacev & Yakshi Dabas & Matthew R. Paul & Christian Pacheco & Michelle Mitchener & Yekaterina Perez & Yan Fang & Alexey A. Soshnev & Douglas Barrows & Thomas Carroll & Nicholas D. Socci & S, 2024. "Cancer-associated Histone H3 N-terminal arginine mutations disrupt PRC2 activity and impair differentiation," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    4. Mădălina Preda & Bogdan Cosmin Tănase & Daniela Luminița Zob & Adelina Silvana Gheorghe & Cristian Virgil Lungulescu & Elena Adriana Dumitrescu & Dana Lucia Stănculeanu & Loredana Sabina Cornelia Mano, 2023. "The Bidirectional Relationship between Pulmonary Tuberculosis and Lung Cancer," IJERPH, MDPI, vol. 20(2), pages 1-13, January.
    5. Prakruti R. Singh & Venkatareddy Dadireddy & Shubha Udupa & Shashwath Malli Kalladi & Somnath Shee & Sanjeev Khosla & Raju S. Rajmani & Amit Singh & Suryanarayanarao Ramakumar & Valakunja Nagaraja, 2023. "The Mycobacterium tuberculosis methyltransferase Rv2067c manipulates host epigenetic programming to promote its own survival," Nature Communications, Nature, vol. 14(1), pages 1-17, 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_s41467-023-37148-x. 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.