IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-30374-9.html
   My bibliography  Save this article

PI(18:1/18:1) is a SCD1-derived lipokine that limits stress signaling

Author

Listed:
  • Maria Thürmer

    (Friedrich-Schiller-University Jena)

  • André Gollowitzer

    (University of Innsbruck)

  • Helmut Pein

    (Friedrich-Schiller-University Jena)

  • Konstantin Neukirch

    (University of Innsbruck)

  • Elif Gelmez

    (Friedrich-Schiller-University Jena)

  • Lorenz Waltl

    (University of Innsbruck)

  • Natalie Wielsch

    (Max Planck Institute for Chemical Ecology)

  • René Winkler

    (Friedrich-Schiller-University Jena)

  • Konstantin Löser

    (Friedrich-Schiller-University Jena)

  • Julia Grander

    (University of Innsbruck)

  • Madlen Hotze

    (University of Innsbruck)

  • Sönke Harder

    (University Medical Center Hamburg-Eppendorf)

  • Annika Döding

    (University Hospital Jena, Friedrich-Schiller-University Jena)

  • Martina Meßner

    (Pharmaceutical Biology, LMU Munich
    Paracelsus Medical University)

  • Fabiana Troisi

    (Friedrich-Schiller-University Jena)

  • Maximilian Ardelt

    (Pharmaceutical Biology, LMU Munich
    Paracelsus Medical University)

  • Hartmut Schlüter

    (University Medical Center Hamburg-Eppendorf)

  • Johanna Pachmayr

    (Pharmaceutical Biology, LMU Munich
    Paracelsus Medical University)

  • Óscar Gutiérrez-Gutiérrez

    (Leibniz Institute on Aging—Fritz Lipmann Institute (FLI))

  • Karl Lenhard Rudolph

    (Leibniz Institute on Aging—Fritz Lipmann Institute (FLI))

  • Kathrin Thedieck

    (University of Innsbruck
    University of Groningen, University Medical Center Groningen
    Carl von Ossietzky University Oldenburg)

  • Ulrike Schulze-Späte

    (University Hospital Jena, Friedrich-Schiller-University Jena)

  • Cristina González-Estévez

    (Leibniz Institute on Aging—Fritz Lipmann Institute (FLI)
    University of Barcelona
    Institute of Biomedicine of the University of Barcelona (IBUB))

  • Christian Kosan

    (Friedrich-Schiller-University Jena)

  • Aleš Svatoš

    (Max Planck Institute for Chemical Ecology)

  • Marcel Kwiatkowski

    (University of Innsbruck)

  • Andreas Koeberle

    (Friedrich-Schiller-University Jena
    University of Innsbruck)

Abstract

Cytotoxic stress activates stress-activated kinases, initiates adaptive mechanisms, including the unfolded protein response (UPR) and autophagy, and induces programmed cell death. Fatty acid unsaturation, controlled by stearoyl-CoA desaturase (SCD)1, prevents cytotoxic stress but the mechanisms are diffuse. Here, we show that 1,2-dioleoyl-sn-glycero-3-phospho-(1’-myo-inositol) [PI(18:1/18:1)] is a SCD1-derived signaling lipid, which inhibits p38 mitogen-activated protein kinase activation, counteracts UPR, endoplasmic reticulum-associated protein degradation, and apoptosis, regulates autophagy, and maintains cell morphology and proliferation. SCD1 expression and the cellular PI(18:1/18:1) proportion decrease during the onset of cell death, thereby repressing protein phosphatase 2 A and enhancing stress signaling. This counter-regulation applies to mechanistically diverse death-inducing conditions and is found in multiple human and mouse cell lines and tissues of Scd1-defective mice. PI(18:1/18:1) ratios reflect stress tolerance in tumorigenesis, chemoresistance, infection, high-fat diet, and immune aging. Together, PI(18:1/18:1) is a lipokine that links fatty acid unsaturation with stress responses, and its depletion evokes stress signaling.

Suggested Citation

  • Maria Thürmer & André Gollowitzer & Helmut Pein & Konstantin Neukirch & Elif Gelmez & Lorenz Waltl & Natalie Wielsch & René Winkler & Konstantin Löser & Julia Grander & Madlen Hotze & Sönke Harder & A, 2022. "PI(18:1/18:1) is a SCD1-derived lipokine that limits stress signaling," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30374-9
    DOI: 10.1038/s41467-022-30374-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-30374-9
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-30374-9?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. Nicholas A. Bishop & Tao Lu & Bruce A. Yankner, 2010. "Neural mechanisms of ageing and cognitive decline," Nature, Nature, vol. 464(7288), pages 529-535, March.
    2. Pui-Mun Wong & Yan Feng & Junru Wang & Rong Shi & Xuejun Jiang, 2015. "Regulation of autophagy by coordinated action of mTORC1 and protein phosphatase 2A," Nature Communications, Nature, vol. 6(1), pages 1-11, November.
    3. Manish Chamoli & Anita Goyala & Syed Shamsh Tabrez & Atif Ahmed Siddiqui & Anupama Singh & Adam Antebi & Gordon J. Lithgow & Jennifer L. Watts & Arnab Mukhopadhyay, 2020. "Polyunsaturated fatty acids and p38-MAPK link metabolic reprogramming to cytoprotective gene expression during dietary restriction," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    4. Wenming Li & Jinqiu Zhu & Juan Dou & Hua She & Kai Tao & Haidong Xu & Qian Yang & Zixu Mao, 2017. "Phosphorylation of LAMP2A by p38 MAPK couples ER stress to chaperone-mediated autophagy," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
    5. Gilbert Di Paolo & Pietro De Camilli, 2006. "Phosphoinositides in cell regulation and membrane dynamics," Nature, Nature, vol. 443(7112), pages 651-657, October.
    6. Yasuaki Itoh & Yuji Kawamata & Masataka Harada & Makoto Kobayashi & Ryo Fujii & Shoji Fukusumi & Kazuhiro Ogi & Masaki Hosoya & Yasuhiro Tanaka & Hiroshi Uejima & Hideyuki Tanaka & Minoru Maruyama & R, 2003. "Free fatty acids regulate insulin secretion from pancreatic β cells through GPR40," Nature, Nature, vol. 422(6928), pages 173-176, March.
    7. Johanna Flach & Sietske T. Bakker & Mary Mohrin & Pauline C. Conroy & Eric M. Pietras & Damien Reynaud & Silvia Alvarez & Morgan E. Diolaiti & Fernando Ugarte & E. Camilla Forsberg & Michelle M. Le Be, 2014. "Replication stress is a potent driver of functional decline in ageing haematopoietic stem cells," Nature, Nature, vol. 512(7513), pages 198-202, August.
    8. Yonghong Bai & Jason G. McCoy & Elena J. Levin & Pablo Sobrado & Kanagalaghatta R. Rajashankar & Brian G. Fox & Ming Zhou, 2015. "X-ray structure of a mammalian stearoyl-CoA desaturase," Nature, Nature, vol. 524(7564), pages 252-256, August.
    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. Samim Sharifi & Prerana Chaudhari & Asya Martirosyan & Alexander Otto Eberhardt & Finja Witt & André Gollowitzer & Lisa Lange & Yvonne Woitzat & Eberechukwu Maryann Okoli & Huahui Li & Norman Rahnis &, 2024. "Reducing the metabolic burden of rRNA synthesis promotes healthy longevity in Caenorhabditis elegans," 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. Yue Huang & Ruipeng Mu & David Wen & Joseph S Grimsby & Meina Liang & Anton I Rosenbaum, 2021. "Differences in levels of phosphatidylinositols in healthy and stable Coronary Artery Disease subjects revealed by HILIC-MRM method with SERRF normalization," PLOS ONE, Public Library of Science, vol. 16(6), pages 1-14, June.
    2. Antonio L Egea-Jiménez & Ángel Pérez-Lara & Senena Corbalán-García & Juan C Gómez-Fernández, 2013. "Phosphatidylinositol 4,5-Bisphosphate Decreases the Concentration of Ca2+, Phosphatidylserine and Diacylglycerol Required for Protein Kinase C α to Reach Maximum Activity," PLOS ONE, Public Library of Science, vol. 8(7), pages 1-8, July.
    3. Sofia Seinfeld & Maria V. Sanchez-Vives, 2015. "Healthy Aging Promotion through Neuroscientific Information-Based Strategies," IJERPH, MDPI, vol. 12(10), pages 1-13, September.
    4. Narasaiah Kovuru & Makiko Mochizuki-Kashio & Theresa Menna & Greer Jeffrey & Yuning Hong & Young me Yoon & Zhe Zhang & Peter Kurre, 2024. "Deregulated protein homeostasis constrains fetal hematopoietic stem cell pool expansion in Fanconi anemia," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    5. Karl-Heinz Tomaszowski & Sunetra Roy & Carolina Guerrero & Poojan Shukla & Caezaan Keshvani & Yue Chen & Martina Ott & Xiaogang Wu & Jianhua Zhang & Courtney D. DiNardo & Detlev Schindler & Katharina , 2023. "Hypomorphic Brca2 and Rad51c double mutant mice display Fanconi anemia, cancer and polygenic replication stress," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    6. Nilmani Singh & Adriana Reyes-Ordoñez & Michael A. Compagnone & Jesus F. Moreno & Benjamin J. Leslie & Taekjip Ha & Jie Chen, 2021. "Redefining the specificity of phosphoinositide-binding by human PH domain-containing proteins," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    7. Emmanuel A. Ayeni & Ahmad M. Aldossary & Daniel A. Ayejoto & Lanre A. Gbadegesin & Abdullah A. Alshehri & Haya A. Alfassam & Henok K. Afewerky & Fahad A. Almughem & Saidu M. Bello & Essam A. Tawfik, 2022. "Neurodegenerative Diseases: Implications of Environmental and Climatic Influences on Neurotransmitters and Neuronal Hormones Activities," IJERPH, MDPI, vol. 19(19), pages 1-24, September.
    8. Di-Ao Liu & Kai Tao & Bin Wu & Ziyan Yu & Malwina Szczepaniak & Matthew Rames & Changsong Yang & Tatyana Svitkina & Yueyao Zhu & Fengyuan Xu & Xiaolin Nan & Wei Guo, 2023. "A phosphoinositide switch mediates exocyst recruitment to multivesicular endosomes for exosome secretion," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    9. Filipe Rodrigues & Christophe Domingos & Diogo Monteiro & Pedro Morouço, 2022. "A Review on Aging, Sarcopenia, Falls, and Resistance Training in Community-Dwelling Older Adults," IJERPH, MDPI, vol. 19(2), pages 1-11, January.
    10. 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.
    11. Jacqueline Feyen & Zhen Ping & Lanpeng Chen & Claire Dijk & Tim V. D. Tienhoven & Paulina M. H. Strien & Remco M. Hoogenboezem & Michiel J. W. Wevers & Mathijs A. Sanders & Ivo P. Touw & Marc H. G. P., 2022. "Myeloid cells promote interferon signaling-associated deterioration of the hematopoietic system," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    12. Małgorzata Marjańska & Uzay E Emir & Dinesh K Deelchand & Melissa Terpstra, 2013. "Faster Metabolite 1H Transverse Relaxation in the Elder Human Brain," PLOS ONE, Public Library of Science, vol. 8(10), pages 1-1, October.
    13. Jing-Yi Ai & Feng-Tzu Chen & Shu-Shih Hsieh & Shih-Chun Kao & Ai-Guo Chen & Tsung-Min Hung & Yu-Kai Chang, 2021. "The Effect of Acute High-Intensity Interval Training on Executive Function: A Systematic Review," IJERPH, MDPI, vol. 18(7), pages 1-17, March.
    14. Hsiao-Lan Sharon Wang & Rongjun Yu & Yu-Tzu Wu & Wen-Yuan Lee & Ming-Fan Lin & Chia-Yuan Chen & Ein-Yiao Shen, 2013. "The Changes of Cerebral Morphology Related to Aging in Taiwanese Population," PLOS ONE, Public Library of Science, vol. 8(1), pages 1-6, January.
    15. Pradeep Ramalingam & Michael C. Gutkin & Michael G. Poulos & Taylor Tillery & Chelsea Doughty & Agatha Winiarski & Ana G. Freire & Shahin Rafii & David Redmond & Jason M. Butler, 2023. "Restoring bone marrow niche function rejuvenates aged hematopoietic stem cells by reactivating the DNA Damage Response," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    16. Darshini Jeyasimman & Bilge Ercan & Dennis Dharmawan & Tomoki Naito & Jingbo Sun & Yasunori Saheki, 2021. "PDZD-8 and TEX-2 regulate endosomal PI(4,5)P2 homeostasis via lipid transport to promote embryogenesis in C. elegans," Nature Communications, Nature, vol. 12(1), pages 1-21, December.
    17. Salome Funes & Jonathan Jung & Del Hayden Gadd & Michelle Mosqueda & Jianjun Zhong & Shankaracharya & Matthew Unger & Karly Stallworth & Debra Cameron & Melissa S. Rotunno & Pepper Dawes & Megan Fowle, 2024. "Expression of ALS-PFN1 impairs vesicular degradation in iPSC-derived microglia," Nature Communications, Nature, vol. 15(1), pages 1-25, December.
    18. Seiichi Koike & Reinhard Jahn, 2024. "Rab GTPases and phosphoinositides fine-tune SNAREs dependent targeting specificity of intracellular vesicle traffic," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    19. Xue Guo & Jianxiu Zhang & Lei Han & Juliet Lee & Shoshana C. Williams & Allison Forsberg & Yan Xu & Rachel Narehood Austin & Liang Feng, 2023. "Structure and mechanism of the alkane-oxidizing enzyme AlkB," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    20. Lie Wang & Ming Zhou, 2023. "Structure of a eukaryotic cholinephosphotransferase-1 reveals mechanisms of substrate recognition and catalysis," Nature Communications, Nature, vol. 14(1), pages 1-8, 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_s41467-022-30374-9. 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.