Activation of lipophagy is required for RAB7 to regulate ferroptosis in sepsis-induced acute kidney injury.

Sepsis-induced acute kidney injury (S-AKI) is the most common type of acute kidney injury (AKI), accompanied by elevated morbidity and mortality rates. This study investigated the mechanism by which lipid droplets (LDs) degraded via autophagy (lipophagy)required for RAB7 regulated ferroptosis in the pathogenesis of S-AKI. Here, we constructed the S-AKI model in vitro and in vivo to elucidate the potential relationship of lipophagy and ferroptosis, and we first confirmed that the activation of lipophagy promoted renal tubular epithelial cell ferroptosis and renal damage in S-AKI. The results showed that lipopolysaccharide (LPS) induced a marked increase in lipid peroxidation and ferroptosis, which were rescued by ferrstain-1 (Fer-1), an inhibitor of ferroptosis. In addition, LPS induced the remarkable activation of RAB7-mediated lipophagy. Importantly, silencing RAB7 alleviated LPS-induced lipid peroxidation and ferroptosis. Thus, the present study demonstrated the potential significant role of ferroptosis and lipophagy in sepsis-induced AKI, and contributed to better understanding of the pathogenesis and treatment targets of AKI. Copyright © 2024 Elsevier Inc. All rights reserved.

Citation

Yuanting Yang, Qisheng Lin, Xuying Zhu, Xinghua Shao, Shu Li, Jialin Li, Jingkui Wu, Haijiao Jin, Chaojun Qi, Na Jiang, Kaiqi Zhang, Qin Wang, Leyi Gu, Zhaohui Ni. Activation of lipophagy is required for RAB7 to regulate ferroptosis in sepsis-induced acute kidney injury. Free radical biology & medicine. 2024 Jun;218:120-131

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PMID: 38583680

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