IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-33735-6.html
   My bibliography  Save this article

TLCD1 and TLCD2 regulate cellular phosphatidylethanolamine composition and promote the progression of non-alcoholic steatohepatitis

Author

Listed:
  • Kasparas Petkevicius

    (AstraZeneca
    AstraZeneca)

  • Henrik Palmgren

    (AstraZeneca
    University of Gothenburg)

  • Matthew S. Glover

    (AstraZeneca)

  • Andrea Ahnmark

    (AstraZeneca)

  • Anne-Christine Andréasson

    (AstraZeneca)

  • Katja Madeyski-Bengtson

    (AstraZeneca)

  • Hiroki Kawana

    (The University of Tokyo
    Advanced Research & Development Programs for Medical Innovation (AMED-LEAP))

  • Erik L. Allman

    (AstraZeneca)

  • Delaney Kaper

    (University of Gothenburg)

  • Martin Uhrbom

    (AstraZeneca)

  • Liselotte Andersson

    (AstraZeneca)

  • Leif Aasehaug

    (AstraZeneca)

  • Johan Forsström

    (AstraZeneca)

  • Simonetta Wallin

    (AstraZeneca)

  • Ingela Ahlstedt

    (AstraZeneca)

  • Renata Leke

    (AstraZeneca)

  • Daniel Karlsson

    (AstraZeneca)

  • Hernán González-King

    (AstraZeneca)

  • Lars Löfgren

    (AstraZeneca)

  • Ralf Nilsson

    (AstraZeneca)

  • Giovanni Pellegrini

    (AstraZeneca)

  • Nozomu Kono

    (The University of Tokyo)

  • Junken Aoki

    (The University of Tokyo
    Advanced Research & Development Programs for Medical Innovation (AMED-LEAP))

  • Sonja Hess

    (AstraZeneca)

  • Grzegorz Sienski

    (AstraZeneca)

  • Marc Pilon

    (University of Gothenburg)

  • Mohammad Bohlooly-Y

    (AstraZeneca)

  • Marcello Maresca

    (AstraZeneca)

  • Xiao-Rong Peng

    (AstraZeneca)

Abstract

The fatty acid composition of phosphatidylethanolamine (PE) determines cellular metabolism, oxidative stress, and inflammation. However, our understanding of how cells regulate PE composition is limited. Here, we identify a genetic locus on mouse chromosome 11, containing two poorly characterized genes Tlcd1 and Tlcd2, that strongly influences PE composition. We generated Tlcd1/2 double-knockout (DKO) mice and found that they have reduced levels of hepatic monounsaturated fatty acid (MUFA)-containing PE species. Mechanistically, TLCD1/2 proteins act cell intrinsically to promote the incorporation of MUFAs into PEs. Furthermore, TLCD1/2 interact with the mitochondria in an evolutionarily conserved manner and regulate mitochondrial PE composition. Lastly, we demonstrate the biological relevance of our findings in dietary models of metabolic disease, where Tlcd1/2 DKO mice display attenuated development of non-alcoholic steatohepatitis compared to controls. Overall, we identify TLCD1/2 proteins as key regulators of cellular PE composition, with our findings having broad implications in understanding and treating disease.

Suggested Citation

  • Kasparas Petkevicius & Henrik Palmgren & Matthew S. Glover & Andrea Ahnmark & Anne-Christine Andréasson & Katja Madeyski-Bengtson & Hiroki Kawana & Erik L. Allman & Delaney Kaper & Martin Uhrbom & Lis, 2022. "TLCD1 and TLCD2 regulate cellular phosphatidylethanolamine composition and promote the progression of non-alcoholic steatohepatitis," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33735-6
    DOI: 10.1038/s41467-022-33735-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-33735-6
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-33735-6?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. Suneng Fu & Ling Yang & Ping Li & Oliver Hofmann & Lee Dicker & Winston Hide & Xihong Lin & Steven M. Watkins & Alexander R. Ivanov & Gökhan S. Hotamisligil, 2011. "Aberrant lipid metabolism disrupts calcium homeostasis causing liver endoplasmic reticulum stress in obesity," Nature, Nature, vol. 473(7348), pages 528-531, May.
    2. John S. O’Neill & Akhilesh B. Reddy, 2011. "Circadian clocks in human red blood cells," Nature, Nature, vol. 469(7331), pages 498-503, January.
    3. Songyuan Li & Nina Akrap & Silvia Cerboni & Michelle J. Porritt & Sandra Wimberger & Anders Lundin & Carl Möller & Mike Firth & Euan Gordon & Bojana Lazovic & Aleksandra Sieńska & Luna Simona Pane & M, 2021. "Universal toxin-based selection for precise genome engineering in human cells," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    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. Martin Peterka & Nina Akrap & Songyuan Li & Sandra Wimberger & Pei-Pei Hsieh & Dmitrii Degtev & Burcu Bestas & Jack Barr & Stijn Plassche & Patricia Mendoza-Garcia & Saša Šviković & Grzegorz Sienski &, 2022. "Harnessing DSB repair to promote efficient homology-dependent and -independent prime editing," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    2. Burcu Bestas & Sandra Wimberger & Dmitrii Degtev & Alexandra Madsen & Antje K. Rottner & Fredrik Karlsson & Sergey Naumenko & Megan Callahan & Julia Liz Touza & Margherita Francescatto & Carl Ivar Möl, 2023. "A Type II-B Cas9 nuclease with minimized off-targets and reduced chromosomal translocations in vivo," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Güneş Parlakgül & Song Pang & Leonardo L. Artico & Nina Min & Erika Cagampan & Reyna Villa & Renata L. S. Goncalves & Grace Yankun Lee & C. Shan Xu & Gökhan S. Hotamışlıgil & Ana Paula Arruda, 2024. "Spatial mapping of hepatic ER and mitochondria architecture reveals zonated remodeling in fasting and obesity," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    4. Marion Rosello & Malo Serafini & Luca Mignani & Dario Finazzi & Carine Giovannangeli & Marina C. Mione & Jean-Paul Concordet & Filippo Del Bene, 2022. "Disease modeling by efficient genome editing using a near PAM-less base editor in vivo," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    5. Sébastien Levesque & Diana Mayorga & Jean-Philippe Fiset & Claudia Goupil & Alexis Duringer & Andréanne Loiselle & Eva Bouchard & Daniel Agudelo & Yannick Doyon, 2022. "Marker-free co-selection for successive rounds of prime editing in human cells," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    6. Sandra Wimberger & Nina Akrap & Mike Firth & Johan Brengdahl & Susanna Engberg & Marie K. Schwinn & Michael R. Slater & Anders Lundin & Pei-Pei Hsieh & Songyuan Li & Silvia Cerboni & Jonathan Sumner &, 2023. "Simultaneous inhibition of DNA-PK and Polϴ improves integration efficiency and precision of genome editing," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    7. I. F. Schene & I. P. Joore & J. H. L. Baijens & R. Stevelink & G. Kok & S. Shehata & E. F. Ilcken & E. C. M. Nieuwenhuis & D. P. Bolhuis & R. C. M. Rees & S. A. Spelier & H. P. J. Doef & J. M. Beekman, 2022. "Mutation-specific reporter for optimization and enrichment of prime editing," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    8. Dmitrii Degtev & Jack Bravo & Aikaterini Emmanouilidi & Aleksandar Zdravković & Oi Kuan Choong & Julia Liz Touza & Niklas Selfjord & Isabel Weisheit & Margherita Francescatto & Pinar Akcakaya & Michel, 2024. "Engineered PsCas9 enables therapeutic genome editing in mouse liver with lipid nanoparticles," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    9. Shiyan Liu & Mutian Chen & Yichang Wang & Yuqing Lei & Ting Huang & Yabin Zhang & Sin Man Lam & Huihui Li & Shiqian Qi & Jia Geng & Kefeng Lu, 2023. "The ER calcium channel Csg2 integrates sphingolipid metabolism with autophagy," Nature Communications, Nature, vol. 14(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_s41467-022-33735-6. 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.