Details

Autor(en) / Beteiligte

• Poindessous, Virginie
• Lazareth, Helene
• Crambert, Gilles
• Cheval, Lydie
• Sampaio, Julio L.
• Pallet, Nicolas

Titel

STAT3 drives the expression of ACSL4 in acute kidney injury

Ist Teil von

• iScience, 2024-06, Vol.27 (6), p.109737-109737, Article 109737

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2024

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Long-chain acyl-CoA synthetase family 4 (ACSL4) metabolizes long-chain polyunsaturated fatty acids (PUFAs), enriching cell membranes with phospholipids susceptible to peroxidation and drive ferroptosis. The role of ACSL4 and ferroptosis upon endoplasmic-reticulum (ER)-stress-induced acute kidney injury (AKI) is unknown. We used lipidomic, molecular, and cellular biology approaches along with a mouse model of AKI induced by ER stress to investigate the role of ACSL4 regulation in membrane lipidome remodeling in the injured tubular epithelium. Tubular epithelial cells (TECs) activate ACSL4 in response to STAT3 signaling. In this context, TEC membrane lipidome is remodeled toward PUFA-enriched triglycerides instead of PUFA-bearing phospholipids. TECs expressing ACSL4 in this setting are not vulnerable to ferroptosis. Thus, ACSL4 activity in TECs is driven by STAT3 signaling, but ACSL4 alone is not enough to sensitize ferroptosis, highlighting the significance of the biological context associated with the study model. [Display omitted] •ACSL4 expression is induced in ER-stressed kidney tubular cells in vivo but not in vitro•ACSL4 is upregulated in response to STAT3 signaling•In this context, TECs lipidome is remodeled toward PUFA-enriched triglycerides•TECs expressing ACSL4 in this setting are not vulnerable to ferroptosis Pathophysiology; Integrative aspects of cell biology; Omics