Interferon gamma induced-ACSL5 shapes the lipidome of kidney tubular cells
Year: 2025
Type: article
Abstract: 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.
Source: iScience
Institutions: Inserm, Université Paris Cité, Centre de Recherche des Cordeliers, Institut Curie, Centre National de la Recherche Scientifique, Structure fédérative de recherche Necker, KU Leuven, Hôpital Necker-Enfants Malades, Assistance Publique – Hôpitaux de Paris, Hôpital Européen Georges-Pompidou
Language: English
Subfield: Biochemistry
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,240
OpenAlex ID: W4410629670