دورية أكاديمية
PCYT2-regulated lipid biosynthesis is critical to muscle health and ageing
| العنوان: | PCYT2-regulated lipid biosynthesis is critical to muscle health and ageing |
|---|---|
| المؤلفون: | Cikes, Domagoj, Elsayad, Kareem, Sezgin, Erdinc, Koitai, Erika, Ferenc, Torma, Orthofer, Michael, Yarwood, Rebecca, Heinz, Leonhard X., Sedlyarov, Vitaly, Darwish-Miranda, Nasser, Taylor, Adrian, Grapentine, Sophie, al-Murshedi, Fathiya, Abot, Anne, Weidinger, Adelheid, Kutchukian, Candice, Sanchez, Colline, Cronin, Shane J. F., Novatchkova, Maria, Kavirayani, Anoop, Schuetz, Thomas, Haubner, Bernhard, Haas, Lisa, Hagelkruys, Astrid, Jackowski, Suzanne, Kozlov, Andrey, Jacquemond, Vincent, Knauf, Claude, Superti-Furga, Giulio, Rullman, Eric, Gustafsson, Thomas, McDermot, John, Lowe, Martin, Radak, Zsolt, Chamberlain, Jeffrey S., Bakovic, Marica, Banka, Siddharth, Penninger, Josef M. |
| المصدر: | Cikes D, Elsayad K, Sezgin E, et al. PCYT2-regulated lipid biosynthesis is critical to muscle health and ageing. Nature Metabolism . 2023;5:495-515. doi: 10.1038/s42255-023-00766-2 |
| بيانات النشر: | Springer Nature |
| سنة النشر: | 2023 |
| المجموعة: | IST Austria Research Explorer (Institute of Science and Technology) |
| مصطلحات موضوعية: | Cell Biology, Physiology (medical), Endocrinology, Diabetes and Metabolism, Internal Medicine |
| الوصف: | Muscle degeneration is the most prevalent cause for frailty and dependency in inherited diseases and ageing. Elucidation of pathophysiological mechanisms, as well as effective treatments for muscle diseases, represents an important goal in improving human health. Here, we show that the lipid synthesis enzyme phosphatidylethanolamine cytidyltransferase (PCYT2/ECT) is critical to muscle health. Human deficiency in PCYT2 causes a severe disease with failure to thrive and progressive weakness. pcyt2-mutant zebrafish and muscle-specific Pcyt2-knockout mice recapitulate the participant phenotypes, with failure to thrive, progressive muscle weakness and accelerated ageing. Mechanistically, muscle Pcyt2 deficiency affects cellular bioenergetics and membrane lipid bilayer structure and stability. PCYT2 activity declines in ageing muscles of mice and humans, and adeno-associated virus-based delivery of PCYT2 ameliorates muscle weakness in Pcyt2-knockout and old mice, offering a therapy for individuals with a rare disease and muscle ageing. Thus, PCYT2 plays a fundamental and conserved role in vertebrate muscle health, linking PCYT2 and PCYT2-synthesized lipids to severe muscle dystrophy and ageing. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/issn/2522-5812; info:eu-repo/semantics/altIdentifier/wos/000992064000002; info:eu-repo/semantics/altIdentifier/pmid/36941451; https://research-explorer.ista.ac.at/record/12747Test |
| الإتاحة: | https://doi.org/10.1038/s42255-023-00766-2Test https://research-explorer.ista.ac.at/record/12747Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.9AB6402C |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |