Interferon gamma induced-ACSL5 shapes the lipidome of kidney tubular cells
Summary: Acyl-CoA synthetase long-chain family (ACSL) enzymes are critical in the activation of long-chain fatty acid. To determine the regulatory mechanisms of ACSL5 and its biological functions within the kidney tubule, we generated transcriptomic, metabolomic, and lipidomic data from experimental...
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Elsevier
2025-06-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S258900422501003X |
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| author | Virginie Poindessous Julio L. Sampaio Lydia Bouidghaghen Ivan Nemazanyy Alexandre Pallet Maarten Naesens Thibaut Vaulet Dany Anglicheau Nicolas Pallet |
| author_facet | Virginie Poindessous Julio L. Sampaio Lydia Bouidghaghen Ivan Nemazanyy Alexandre Pallet Maarten Naesens Thibaut Vaulet Dany Anglicheau Nicolas Pallet |
| author_sort | Virginie Poindessous |
| collection | DOAJ |
| description | Summary: Acyl-CoA synthetase long-chain family (ACSL) enzymes are critical in the activation of long-chain fatty acid. To determine the regulatory mechanisms of ACSL5 and its biological functions within the kidney tubule, we generated transcriptomic, metabolomic, and lipidomic data from experimental models and patient cohorts. We show that ACSL5 is a constituent of a gamma interferon-related gene signature linked to rejection in kidney transplant recipients and the urinary metabolome of kidney transplant recipients who experienced rejection exhibited a deficiency in ACSL5 substrates. We demonstrate that ACSL5 expression is induced in kidney tubular cells in response to IRF-1 signaling, and that it is involved in maintaining ATP production and cell viability and influences their lipid composition, reducing the accumulation of ceramides and the contents in glycerolipids. Thus, modulation of the activity of ACSL5 could impact tubular cell energy metabolism and lipid composition, with a clinical impact in response to kidney allograft injury. |
| format | Article |
| id | doaj-art-e7174a9f286245fba5ed634c76b58d76 |
| institution | OA Journals |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-e7174a9f286245fba5ed634c76b58d762025-08-20T02:05:36ZengElsevieriScience2589-00422025-06-0128611274210.1016/j.isci.2025.112742Interferon gamma induced-ACSL5 shapes the lipidome of kidney tubular cellsVirginie Poindessous0Julio L. Sampaio1Lydia Bouidghaghen2Ivan Nemazanyy3Alexandre Pallet4Maarten Naesens5Thibaut Vaulet6Dany Anglicheau7Nicolas Pallet8Centre de Recherche des Cordeliers, INSERM UMRS1138, Université Paris Cité, Paris, FranceCurieCoreTech Metabolomics and Lipidomics Technology Platform, Institut Curie, Paris, FranceCurieCoreTech Metabolomics and Lipidomics Technology Platform, Institut Curie, Paris, FrancePlatform for Metabolic Analyses, Structure Fédérative de Recherche Necker, INSERM US24/CNRS UMS 3633, Paris, FranceCentre de Recherche des Cordeliers, INSERM UMRS1138, Université Paris Cité, Paris, FranceDepartment of Microbiology, Immunology and Transplantation, Nephrology and Kidney Transplantation Research Group, KU Leuven, Leuven, BelgiumDepartment of Microbiology, Immunology and Transplantation, Nephrology and Kidney Transplantation Research Group, KU Leuven, Leuven, BelgiumDepartment of Kidney and Metabolic Diseases, Transplantation and Clinical Immunology, Necker Hospital, Assistance Publique - Hôpitaux de Paris Université Paris Cité, Paris, FranceCentre de Recherche des Cordeliers, INSERM UMRS1138, Université Paris Cité, Paris, France; Department of Nephrology, Georges Pompidou European Hospital, Assistance Publique Hôpitaux de Paris, Université Paris Cité, Paris, France; Department of Clinical Chemistry, Georges Pompidou European Hospital, Assistance Publique Hôpitaux de Paris, Université Paris Cité, Paris, France; Corresponding authorSummary: Acyl-CoA synthetase long-chain family (ACSL) enzymes are critical in the activation of long-chain fatty acid. To determine the regulatory mechanisms of ACSL5 and its biological functions within the kidney tubule, we generated transcriptomic, metabolomic, and lipidomic data from experimental models and patient cohorts. We show that ACSL5 is a constituent of a gamma interferon-related gene signature linked to rejection in kidney transplant recipients and the urinary metabolome of kidney transplant recipients who experienced rejection exhibited a deficiency in ACSL5 substrates. We demonstrate that ACSL5 expression is induced in kidney tubular cells in response to IRF-1 signaling, and that it is involved in maintaining ATP production and cell viability and influences their lipid composition, reducing the accumulation of ceramides and the contents in glycerolipids. Thus, modulation of the activity of ACSL5 could impact tubular cell energy metabolism and lipid composition, with a clinical impact in response to kidney allograft injury.http://www.sciencedirect.com/science/article/pii/S258900422501003XIntegrative aspects of cell biologyLipidomicsMetabolomicsTranscriptomics |
| spellingShingle | Virginie Poindessous Julio L. Sampaio Lydia Bouidghaghen Ivan Nemazanyy Alexandre Pallet Maarten Naesens Thibaut Vaulet Dany Anglicheau Nicolas Pallet Interferon gamma induced-ACSL5 shapes the lipidome of kidney tubular cells iScience Integrative aspects of cell biology Lipidomics Metabolomics Transcriptomics |
| title | Interferon gamma induced-ACSL5 shapes the lipidome of kidney tubular cells |
| title_full | Interferon gamma induced-ACSL5 shapes the lipidome of kidney tubular cells |
| title_fullStr | Interferon gamma induced-ACSL5 shapes the lipidome of kidney tubular cells |
| title_full_unstemmed | Interferon gamma induced-ACSL5 shapes the lipidome of kidney tubular cells |
| title_short | Interferon gamma induced-ACSL5 shapes the lipidome of kidney tubular cells |
| title_sort | interferon gamma induced acsl5 shapes the lipidome of kidney tubular cells |
| topic | Integrative aspects of cell biology Lipidomics Metabolomics Transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S258900422501003X |
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