IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-54958-9.html
   My bibliography  Save this article

Yin Yang 1 and guanine quadruplexes protect dopaminergic neurons from cellular stress via transmissive dormancy

Author

Listed:
  • Kielen R. Zuurbier

    (Department of Molecular Biology; University of Texas Southwestern Medical Center
    UT Southwestern Medical Center)

  • Rene Solano Fonseca

    (Department of Molecular Biology; University of Texas Southwestern Medical Center)

  • Sonja L. B. Arneaud

    (Department of Molecular Biology; University of Texas Southwestern Medical Center)

  • Jordan M. Wall

    (Department of Molecular Biology; University of Texas Southwestern Medical Center)

  • Juhee Kim

    (Department of Molecular Biology; University of Texas Southwestern Medical Center)

  • Lexus Tatge

    (Department of Molecular Biology; University of Texas Southwestern Medical Center)

  • Gupse Otuzoglu

    (Department of Molecular Biology; University of Texas Southwestern Medical Center)

  • Sofia Bali

    (UT Southwestern Medical Center
    UT Southwestern Medical Center)

  • Patrick Metang

    (Department of Molecular Biology; University of Texas Southwestern Medical Center)

  • Peter M. Douglas

    (Department of Molecular Biology; University of Texas Southwestern Medical Center
    UT Southwestern Medical Center
    Hamon Center for Regenerative Science and Medicine; UT Southwestern Medical Center)

Abstract

Neurons deploy diverse adaptive strategies to ensure survival and neurotransmission amid cellular stress. When these adaptive pathways are overwhelmed, functional impairment or neurodegeneration follows. Here we show that stressed neurons actively induce a state of transmissive dormancy as a protective measure. Extending observations of neurotrauma in C. elegans and mice, human dopaminergic neurons capable of surviving severe cellular challenges both decrease spontaneous activity and modulate dopamine homeostasis through the transcriptional regulator Yin Yang 1 (YY1). To bolster stress resilience and mitigate dopamine toxicity, YY1 increases expression of the vesicular monoamine transporter 2, vMAT2, while coordinately inhibiting dopamine synthesis through stabilization of a guanine quadruplex in intron 10 of tyrosine hydroxylase, TH. This dopaminergic stress response has the potential to cause circuit inactivation, yet safeguards neurons by minimizing the toxic accumulation of cytosolic dopamine and inducing a state of neuronal dormancy. In essence, neurons appear to actively prioritize viability over functionality.

Suggested Citation

  • Kielen R. Zuurbier & Rene Solano Fonseca & Sonja L. B. Arneaud & Jordan M. Wall & Juhee Kim & Lexus Tatge & Gupse Otuzoglu & Sofia Bali & Patrick Metang & Peter M. Douglas, 2024. "Yin Yang 1 and guanine quadruplexes protect dopaminergic neurons from cellular stress via transmissive dormancy," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54958-9
    DOI: 10.1038/s41467-024-54958-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-54958-9
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-54958-9?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. Patricia González-Rodríguez & Enrico Zampese & Kristen A. Stout & Jaime N. Guzman & Ema Ilijic & Ben Yang & Tatiana Tkatch & Mihaela A. Stavarache & David L. Wokosin & Lin Gao & Michael G. Kaplitt & J, 2021. "Disruption of mitochondrial complex I induces progressive parkinsonism," Nature, Nature, vol. 599(7886), pages 650-656, November.
    2. Tao Lu & Liviu Aron & Joseph Zullo & Ying Pan & Haeyoung Kim & Yiwen Chen & Tun-Hsiang Yang & Hyun-Min Kim & Derek Drake & X. Shirley Liu & David A. Bennett & Monica P. Colaiácovo & Bruce A. Yankner, 2014. "REST and stress resistance in ageing and Alzheimer’s disease," Nature, Nature, vol. 507(7493), pages 448-454, March.
    3. Ravi S. Kamath & Andrew G. Fraser & Yan Dong & Gino Poulin & Richard Durbin & Monica Gotta & Alexander Kanapin & Nathalie Le Bot & Sergio Moreno & Marc Sohrmann & David P. Welchman & Peder Zipperlen &, 2003. "Systematic functional analysis of the Caenorhabditis elegans genome using RNAi," Nature, Nature, vol. 421(6920), pages 231-237, January.
    4. Guang-Hui Liu & Jing Qu & Keiichiro Suzuki & Emmanuel Nivet & Mo Li & Nuria Montserrat & Fei Yi & Xiuling Xu & Sergio Ruiz & Weiqi Zhang & Ulrich Wagner & Audrey Kim & Bing Ren & Ying Li & April Goebl, 2012. "Progressive degeneration of human neural stem cells caused by pathogenic LRRK2," Nature, Nature, vol. 491(7425), pages 603-607, November.
    5. Stephen P. Jackson & Jiri Bartek, 2009. "The DNA-damage response in human biology and disease," Nature, Nature, vol. 461(7267), pages 1071-1078, October.
    Full references (including those not matched with items on IDEAS)

    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. Baolei Yuan & Xuan Zhou & Keiichiro Suzuki & Gerardo Ramos-Mandujano & Mengge Wang & Muhammad Tehseen & Lorena V. Cortés-Medina & James J. Moresco & Sarah Dunn & Reyna Hernandez-Benitez & Tomoaki Hish, 2022. "Wiskott-Aldrich syndrome protein forms nuclear condensates and regulates alternative splicing," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    2. Shuangshuang Sun & Zhe Xu & Liying He & Yihui Shen & Yuqing Yan & Xubing Lv & Xujing Zhu & Wei Li & Wei-Ya Tian & Yongjun Zheng & Sen Lin & Yadong Sun & Lei Li, 2024. "Metabolic regulation of cytoskeleton functions by HDAC6-catalyzed α-tubulin lactylation," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    3. Zita Gál & Stavroula Boukoura & Kezia Catharina Oxe & Sara Badawi & Blanca Nieto & Lea Milling Korsholm & Sille Blangstrup Geisler & Ekaterina Dulina & Anna Vestergaard Rasmussen & Christina Dahl & We, 2024. "Hyper-recombination in ribosomal DNA is driven by long-range resection-independent RAD51 accumulation," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    4. Ilaria Rosso & Corey Jones-Weinert & Francesca Rossiello & Matteo Cabrini & Silvia Brambillasca & Leonel Munoz-Sagredo & Zeno Lavagnino & Emanuele Martini & Enzo Tedone & Massimiliano Garre’ & Julio A, 2023. "Alternative lengthening of telomeres (ALT) cells viability is dependent on C-rich telomeric RNAs," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    5. Jin-Hyuck Jeong & Jun-Seok Han & Youngae Jung & Seung-Min Lee & So-Hyun Park & Mooncheol Park & Min-Gi Shin & Nami Kim & Mi Sun Kang & Seokho Kim & Kwang-Pyo Lee & Ki-Sun Kwon & Chun-A. Kim & Yong Ryo, 2023. "A new AMPK isoform mediates glucose-restriction induced longevity non-cell autonomously by promoting membrane fluidity," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    6. Ichiro Kawasaki & Kenta Sugiura & Taeko Sasaki & Noriyuki Matsuda & Miyuki Sato & Ken Sato, 2024. "MARC-3, a membrane-associated ubiquitin ligase, is required for fast polyspermy block in Caenorhabditis elegans," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    7. Hope Dang & Raul Castro-Portuguez & Luis Espejo & Grant Backer & Samuel Freitas & Erica Spence & Jeremy Meyers & Karissa Shuck & Emily A. Gardea & Leah M. Chang & Jonah Balsa & Niall Thorns & Caroline, 2023. "On the benefits of the tryptophan metabolite 3-hydroxyanthranilic acid in Caenorhabditis elegans and mouse aging," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    8. Halh Al-Serori & Franziska Ferk & Michael Kundi & Andrea Bileck & Christopher Gerner & Miroslav Mišík & Armen Nersesyan & Monika Waldherr & Manuel Murbach & Tamara T Lah & Christel Herold-Mende & Andr, 2018. "Mobile phone specific electromagnetic fields induce transient DNA damage and nucleotide excision repair in serum-deprived human glioblastoma cells," PLOS ONE, Public Library of Science, vol. 13(4), pages 1-17, April.
    9. Arles Urrutia & Víctor A García-Angulo & Andrés Fuentes & Mauricio Caneo & Marcela Legüe & Sebastián Urquiza & Scarlett E Delgado & Juan Ugalde & Paula Burdisso & Andrea Calixto, 2020. "Bacterially produced metabolites protect C. elegans neurons from degeneration," PLOS Biology, Public Library of Science, vol. 18(3), pages 1-31, March.
    10. Daipayan Banerjee & Kurt Langberg & Salar Abbas & Eric Odermatt & Praveen Yerramothu & Martin Volaric & Matthew A. Reidenbach & Kathy J. Krentz & C. Dustin Rubinstein & David L. Brautigan & Tarek Abba, 2021. "A non-canonical, interferon-independent signaling activity of cGAMP triggers DNA damage response signaling," Nature Communications, Nature, vol. 12(1), pages 1-24, December.
    11. Klement Stojanovski & Ioana Gheorghe & Peter Lenart & Anne Lanjuin & William B. Mair & Benjamin D. Towbin, 2023. "Maintenance of appropriate size scaling of the C. elegans pharynx by YAP-1," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    12. Jenny Kaur Singh & Rebecca Smith & Magdalena B. Rother & Anton J. L. Groot & Wouter W. Wiegant & Kees Vreeken & Ostiane D’Augustin & Robbert Q. Kim & Haibin Qian & Przemek M. Krawczyk & Román González, 2021. "Zinc finger protein ZNF384 is an adaptor of Ku to DNA during classical non-homologous end-joining," Nature Communications, Nature, vol. 12(1), pages 1-21, December.
    13. Miho M. Suzuki & Kenta Iijima & Koichi Ogami & Keiko Shinjo & Yoshiteru Murofushi & Jingqi Xie & Xuebing Wang & Yotaro Kitano & Akira Mamiya & Yuji Kibe & Tatsunori Nishimura & Fumiharu Ohka & Ryuta S, 2023. "TUG1-mediated R-loop resolution at microsatellite loci as a prerequisite for cancer cell proliferation," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    14. Ye Cai & Huifen Cao & Fang Wang & Yufei Zhang & Philipp Kapranov, 2022. "Complex genomic patterns of abasic sites in mammalian DNA revealed by a high-resolution SSiNGLe-AP method," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    15. Kevin Y Yip & Roger P Alexander & Koon-Kiu Yan & Mark Gerstein, 2010. "Improved Reconstruction of In Silico Gene Regulatory Networks by Integrating Knockout and Perturbation Data," PLOS ONE, Public Library of Science, vol. 5(1), pages 1-9, January.
    16. Svenia D. Heinze & Simon Berger & Stefanie Engleitner & Michael Daube & Alex Hajnal, 2023. "Prolonging somatic cell proliferation through constitutive hox gene expression in C. elegans," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    17. Sidrah Shah & Alison Cheung & Mikolaj Kutka & Matin Sheriff & Stergios Boussios, 2022. "Epithelial Ovarian Cancer: Providing Evidence of Predisposition Genes," IJERPH, MDPI, vol. 19(13), pages 1-14, July.
    18. Jérémy Sandoz & Max Cigrang & Amélie Zachayus & Philippe Catez & Lise-Marie Donnio & Clèmence Elly & Jadwiga Nieminuszczy & Pietro Berico & Cathy Braun & Sergey Alekseev & Jean-Marc Egly & Wojciech Ni, 2023. "Active mRNA degradation by EXD2 nuclease elicits recovery of transcription after genotoxic stress," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    19. Jessica D. Tischler & Hiroshi Tsuchida & Rosevalentine Bosire & Tommy T. Oda & Ana Park & Richard O. Adeyemi, 2024. "FLIP(C1orf112)-FIGNL1 complex regulates RAD51 chromatin association to promote viability after replication stress," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    20. Fei Sun & Nourhan Nashat Ali & Daniela Londoño-Vásquez & Constantine A. Simintiras & Huanyu Qiao & M. Sofia Ortega & Yuksel Agca & Masashi Takahashi & Rocío M. Rivera & Andrew M. Kelleher & Peter Suto, 2024. "Increased DNA damage in full-grown oocytes is correlated with diminished autophagy activation," Nature Communications, Nature, vol. 15(1), pages 1-20, 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:15:y:2024:i:1:d:10.1038_s41467-024-54958-9. 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.