GIMAP5 deficiency reveals a mammalian ceramide-driven longevity assurance pathway.

Autor:	Park AY; Molecular Development of the Immune System Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.; Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Leney-Greene M; Molecular Development of the Immune System Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.; Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Lynberg M; Molecular Development of the Immune System Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.; Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Gabrielski JQ; Molecular Development of the Immune System Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.; Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Xu X; Molecular Development of the Immune System Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.; Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Schwarz B; Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA., Zheng L; Molecular Development of the Immune System Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.; Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Balasubramaniyam A; Molecular Development of the Immune System Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.; Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.; Department of Structural Biology, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany., Ham H; Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Chao B; Molecular Development of the Immune System Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.; Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Zhang Y; Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Matthews HF; Molecular Development of the Immune System Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.; Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Cui J; Molecular Development of the Immune System Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.; Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Yao Y; Molecular Development of the Immune System Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.; Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Kubo S; Molecular Development of the Immune System Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.; Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Chanchu JM; Molecular Development of the Immune System Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.; Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Morawski AR; Molecular Development of the Immune System Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.; Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Cook SA; Molecular Development of the Immune System Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.; Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Jiang P; Molecular Development of the Immune System Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.; Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Ravell JC; Molecular Development of the Immune System Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.; Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.; Department of Internal Medicine, Hackensack Meridian School of Medicine, Nutley, NJ, USA., Cheng YH; Molecular Development of the Immune System Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.; Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., George A; Molecular Development of the Immune System Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.; Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Faruqi A; Molecular Development of the Immune System Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.; Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Pagalilauan AM; Molecular Development of the Immune System Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.; Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Bergerson JRE; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Ganesan S; Biological Imaging Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Chauvin SD; Molecular Development of the Immune System Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.; Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Aluri J; Molecular Development of the Immune System Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.; Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Edwards-Hicks J; Department of Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany., Bohrnsen E; Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA., Tippett C; Section of Digestive Diseases, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.; Department of Pathology, Yale School of Medicine, New Haven, CT, USA., Omar H; Molecular Development of the Immune System Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.; Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Xu L; Molecular Development of the Immune System Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.; Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Butcher GW; Laboratory of Lymphocyte Signaling and Development, The Babraham Institute, Cambridge, United Kingdom., Pascall J; Laboratory of Lymphocyte Signaling and Development, The Babraham Institute, Cambridge, United Kingdom., Karakoc-Aydiner E; Division of Pediatric Allergy and Immunology, Marmara University, School of Medicine Pendik, Istanbul, Turkey.; The Isil Berat Barlan Center for Translational Medicine, Marmara University, Pendik, Istanbul, Turkey., Kiykim A; Division of Pediatric Allergy and Immunology, Marmara University, School of Medicine Pendik, Istanbul, Turkey., Maecker H; Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Palo Alto, CA, USA., Tezcan İ; Department of Pediatrics, Division of Pediatric Immunology, Hacettepe University, Faculty of Medicine, Ankara, Turkey., Esenboga S; Department of Pediatrics, Division of Pediatric Immunology, Hacettepe University, Faculty of Medicine, Ankara, Turkey., Heredia RJ; St Anna Children's Cancer Research Institute, Vienna, Austria.; Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria.; Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria., Akata D; Department of Radiology, Faculty of Medicine, Hacettepe University, Ankara, Turkey., Tekin S; Department of Basic Medical Sciences, Hamidiye Faculty of Medicine, Division of Medical Biology, University of Health Sciences, İstanbul, Turkey., Kara A; TUBITAK Marmara Research Center, Gene Engineering and Biotechnology Institute, Gebze, Turkey., Kuloglu Z; Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Ankara University School of Medicine, Ankara, Türkiye., Unal E; Department of Pediatric Oncology, Ankara University Medical School, Ankara, Turkey., Kendirli T; Department of Pediatric Intensive Care Unit, Ankara University Medical School, Ankara, Turkey., Dogu F; Department of Pediatric Immunology and Allergy, Ankara University Medical School, Ankara, Turkey., Karabiber E; Department of Chest Diseases, Faculty of Medicine, Division of Adult Allergy-Immunology, Marmara University, Istanbul, Turkey., Atkinson TP; Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA., Cochet C; University Grenoble Alpes, INSERM, CEA, UMR Biosanté, Grenoble, France., Filhol O; University Grenoble Alpes, INSERM, CEA, UMR Biosanté, Grenoble, France., Bosio CM; Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA., Davis MM; Institute for Immunity, Transplantation and Infection, Stanford University, Palo Alto, CA, USA., Lifton RP; Department of Genetics, Yale School of Medicine, Yale University, New Haven, CT, USA.; Laboratory of Human Genetics and Genomics, The Rockefeller University, New York, NY, USA., Pearce EL; Department of Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.; The Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Johns Hopkins University, Baltimore, MD, USA., Daumke O; Department of Structural Biology, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.; Institute for Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany., Aytekin C; Department of Pediatric Immunology, Dr Sami Ulus Maternity and Children's Health and Diseases Training and Research Hospital, Ankara, Turkey., Şahin GE; Department of Pediatric Gastroenterology, Hepatology and Nutrition, University of Health Sciences, Dr Sami Ulus Maternity and Children's Health and Diseases Training and Research Hospital, Ankara, Turkey., Aksu AÜ; 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Jazyk:	angličtina
Zdroj:	Nature immunology [Nat Immunol] 2024 Feb; Vol. 25 (2), pp. 282-293. Date of Electronic Publication: 2024 Jan 03.
DOI:	10.1038/s41590-023-01691-y
Abstrakt:	Preserving cells in a functional, non-senescent state is a major goal for extending human healthspans. Model organisms reveal that longevity and senescence are genetically controlled, but how genes control longevity in different mammalian tissues is unknown. Here, we report a new human genetic disease that causes cell senescence, liver and immune dysfunction, and early mortality that results from deficiency of GIMAP5, an evolutionarily conserved GTPase selectively expressed in lymphocytes and endothelial cells. We show that GIMAP5 restricts the pathological accumulation of long-chain ceramides (CERs), thereby regulating longevity. GIMAP5 controls CER abundance by interacting with protein kinase CK2 (CK2), attenuating its ability to activate CER synthases. Inhibition of CK2 and CER synthase rescues GIMAP5-deficient T cells by preventing CER overaccumulation and cell deterioration. Thus, GIMAP5 controls longevity assurance pathways crucial for immune function and healthspan in mammals. (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Databáze:	MEDLINE
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