IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-31755-w.html
   My bibliography  Save this article

Nestin-dependent mitochondria-ER contacts define stem Leydig cell differentiation to attenuate male reproductive ageing

Author

Listed:
  • Senyu Yao

    (The Seventh Affiliated Hospital of Sun Yat-sen University
    Sun Yat-Sen University)

  • Xiaoyue Wei

    (The Seventh Affiliated Hospital of Sun Yat-sen University
    Sun Yat-Sen University)

  • Wenrui Deng

    (The Seventh Affiliated Hospital of Sun Yat-sen University
    Sun Yat-Sen University)

  • Boyan Wang

    (The Seventh Affiliated Hospital of Sun Yat-sen University
    Sun Yat-Sen University)

  • Jianye Cai

    (Sun Yat-Sen University
    Sun Yat-Sen University)

  • Yinong Huang

    (Sun Yat-Sen University
    The First Affiliated Hospital of Sun Yat-Sen University)

  • Xiaofan Lai

    (Sun Yat-Sen University
    Sun Yat-sen University)

  • Yuan Qiu

    (Sun Yat-Sen University)

  • Yi Wang

    (Sun Yat-Sen University)

  • Yuanjun Guan

    (Sun Yat-Sen University)

  • Jiancheng Wang

    (The Seventh Affiliated Hospital of Sun Yat-sen University
    Sun Yat-Sen University
    Sun Yat-Sen University)

Abstract

Male reproductive system ageing is closely associated with deficiency in testosterone production due to loss of functional Leydig cells, which are differentiated from stem Leydig cells (SLCs). However, the relationship between SLC differentiation and ageing remains unknown. In addition, active lipid metabolism during SLC differentiation in the reproductive system requires transportation and processing of substrates among multiple organelles, e.g., mitochondria and endoplasmic reticulum (ER), highlighting the importance of interorganelle contact. Here, we show that SLC differentiation potential declines with disordered intracellular homeostasis during SLC senescence. Mechanistically, loss of the intermediate filament Nestin results in lower differentiation capacity by separating mitochondria-ER contacts (MERCs) during SLC senescence. Furthermore, pharmacological intervention by melatonin restores Nestin-dependent MERCs, reverses SLC differentiation capacity and alleviates male reproductive system ageing. These findings not only explain SLC senescence from a cytoskeleton-dependent MERCs regulation mechanism, but also suggest a promising therapy targeting SLC differentiation for age-related reproductive system diseases.

Suggested Citation

  • Senyu Yao & Xiaoyue Wei & Wenrui Deng & Boyan Wang & Jianye Cai & Yinong Huang & Xiaofan Lai & Yuan Qiu & Yi Wang & Yuanjun Guan & Jiancheng Wang, 2022. "Nestin-dependent mitochondria-ER contacts define stem Leydig cell differentiation to attenuate male reproductive ageing," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31755-w
    DOI: 10.1038/s41467-022-31755-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-31755-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-31755-w?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. Dorian V. Ziegler & David Vindrieux & Delphine Goehrig & Sara Jaber & Guillaume Collin & Audrey Griveau & Clotilde Wiel & Nadia Bendridi & Sophia Djebali & Valerio Farfariello & Natacha Prevarskaya & , 2021. "Calcium channel ITPR2 and mitochondria–ER contacts promote cellular senescence and aging," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    2. James D. Phelan & Ryan M. Young & Daniel E. Webster & Sandrine Roulland & George W. Wright & Monica Kasbekar & Arthur L. Shaffer & Michele Ceribelli & James Q. Wang & Roland Schmitz & Masao Nakagawa &, 2018. "A multiprotein supercomplex controlling oncogenic signalling in lymphoma," Nature, Nature, vol. 560(7718), pages 387-391, August.
    3. Michael Segel & Björn Neumann & Myfanwy F. E. Hill & Isabell P. Weber & Carlo Viscomi & Chao Zhao & Adam Young & Chibeza C. Agley & Amelia J. Thompson & Ginez A. Gonzalez & Amar Sharma & Staffan Holmq, 2019. "Author Correction: Niche stiffness underlies the ageing of central nervous system progenitor cells," Nature, Nature, vol. 573(7773), pages 3-3, September.
    4. Jiancheng Wang & Qiying Lu & Jianye Cai & Yi Wang & Xiaofan Lai & Yuan Qiu & Yinong Huang & Qiong Ke & Yanan Zhang & Yuanjun Guan & Haoxiang Wu & Yuanyuan Wang & Xin Liu & Yue Shi & Kang Zhang & Maosh, 2019. "Nestin regulates cellular redox homeostasis in lung cancer through the Keap1–Nrf2 feedback loop," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    5. Michael Segel & Björn Neumann & Myfanwy F. E. Hill & Isabell P. Weber & Carlo Viscomi & Chao Zhao & Adam Young & Chibeza C. Agley & Amelia J. Thompson & Ginez A. Gonzalez & Amar Sharma & Staffan Holmq, 2019. "Niche stiffness underlies the ageing of central nervous system progenitor cells," Nature, Nature, vol. 573(7772), pages 130-134, September.
    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. Ani Chi & Bicheng Yang & Hao Dai & Xinyu Li & Jiahui Mo & Yong Gao & Zhihong Chen & Xin Feng & Menghui Ma & Yanqing Li & Chao Yang & Jie Liu & Hanchao Liu & Zhenqing Wang & Feng Gao & Yan Liao & Xueta, 2024. "Stem Leydig cells support macrophage immunological homeostasis through mitochondrial transfer in mice," Nature Communications, Nature, vol. 15(1), pages 1-18, 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. Xuandi Hou & Jianing Jing & Yizhou Jiang & Xiaohui Huang & Quanxiang Xian & Ting Lei & Jiejun Zhu & Kin Fung Wong & Xinyi Zhao & Min Su & Danni Li & Langzhou Liu & Zhihai Qiu & Lei Sun, 2024. "Nanobubble-actuated ultrasound neuromodulation for selectively shaping behavior in mice," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. Frederic Fiore & Khaleel Alhalaseh & Ram R. Dereddi & Felipe Bodaleo Torres & Ilknur Çoban & Ali Harb & Amit Agarwal, 2023. "Norepinephrine regulates calcium signals and fate of oligodendrocyte precursor cells in the mouse cerebral cortex," Nature Communications, Nature, vol. 14(1), pages 1-25, December.
    3. Patricia R. Pitrez & Luis M. Monteiro & Oliver Borgogno & Xavier Nissan & Jerome Mertens & Lino Ferreira, 2024. "Cellular reprogramming as a tool to model human aging in a dish," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    4. John N. Mariani & Benjamin Mansky & Pernille M. Madsen & Dennis Salinas & Deniz Kesmen & Nguyen P. T. Huynh & Nicholas J. Kuypers & Erin R. Kesel & Janna Bates & Casey Payne & Devin Chandler-Militello, 2024. "Repression of developmental transcription factor networks triggers aging-associated gene expression in human glial progenitor cells," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    5. Samira Ghorbani & Emily Jelinek & Rajiv Jain & Benjamin Buehner & Cenxiao Li & Brian M. Lozinski & Susobhan Sarkar & Deepak K. Kaushik & Yifei Dong & Thomas N. Wight & Soheila Karimi-Abdolrezaee & Gee, 2022. "Versican promotes T helper 17 cytotoxic inflammation and impedes oligodendrocyte precursor cell remyelination," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    6. Timo N. Kohler & Joachim Jonghe & Anna L. Ellermann & Ayaka Yanagida & Michael Herger & Erin M. Slatery & Antonia Weberling & Clara Munger & Katrin Fischer & Carla Mulas & Alex Winkel & Connor Ross & , 2023. "Plakoglobin is a mechanoresponsive regulator of naive pluripotency," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    7. Alerie Guzman de la Fuente & Marie Dittmer & Elise J. Heesbeen & Nira de la Vega Gallardo & Jessica A. White & Andrew Young & Tiree McColgan & Amy Dashwood & Katie Mayne & Sonia Cabeza-Fernández & Joh, 2024. "Ageing impairs the regenerative capacity of regulatory T cells in mouse central nervous system remyelination," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    8. Céline Labouesse & Bao Xiu Tan & Chibeza C. Agley & Moritz Hofer & Alexander K. Winkel & Giuliano G. Stirparo & Hannah T. Stuart & Christophe M. Verstreken & Carla Mulas & William Mansfield & Paul Ber, 2021. "StemBond hydrogels control the mechanical microenvironment for pluripotent stem cells," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    9. Ying Yang & Pekka Paivinen & Chang Xie & Alexis Leigh Krup & Tomi P. Makela & Keith E. Mostov & Jeremy F. Reiter, 2021. "Ciliary Hedgehog signaling patterns the digestive system to generate mechanical forces driving elongation," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    10. Jonathan H. Lam & Nicole Baumgarth, 2023. "Toll-like receptor mediated inflammation directs B cells towards protective antiviral extrafollicular responses," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    11. Bonnie Huang & James D. Phelan & Silvia Preite & Julio Gomez-Rodriguez & Kristoffer H. Johansen & Hirofumi Shibata & Arthur L. Shaffer & Qin Xu & Brendan Jeffrey & Martha Kirby & Stacie Anderson & Yan, 2022. "In vivo CRISPR screens reveal a HIF-1α-mTOR-network regulates T follicular helper versus Th1 cells," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    12. Yandan Yang & Arnold Bolomsky & Thomas Oellerich & Ping Chen & Michele Ceribelli & Björn Häupl & George W. Wright & James D. Phelan & Da Wei Huang & James W. Lord & Callie K. Winkle & Xin Yu & Jan Wis, 2022. "Oncogenic RAS commandeers amino acid sensing machinery to aberrantly activate mTORC1 in multiple myeloma," Nature Communications, Nature, vol. 13(1), pages 1-19, 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:13:y:2022:i:1:d:10.1038_s41467-022-31755-w. 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.