FTO deficiency in older livers exacerbates ferroptosis during ischaemia/reperfusion injury by upregulating ACSL4 and TFRC

• Published in: Nature communications Vol. 15; no. 1; pp. 4760 - 20
• Main Authors: Li, Rong, Yan, Xijing, Xiao, Cuicui, Wang, Tingting, Li, Xuejiao, Hu, Zhongying, Liang, Jinliang, Zhang, Jiebin, Cai, Jianye, Sui, Xin, Liu, Qiuli, Wu, Manli, Xiao, Jiaqi, Chen, Haitian, Liu, Yasong, Jiang, Chenhao, Lv, Guo, Chen, Guihua, Zhang, Yingcai, Yao, Jia, Zheng, Jun, Yang, Yang
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.06.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/1; 13/2; 13/51; 14; 631/136/7; 631/80/82; 692/4020/4021/288/2032; 692/700/565/545/576/402; Alpha-Ketoglutarate-Dependent Dioxygenase FTO - genetics; Alpha-Ketoglutarate-Dependent Dioxygenase FTO - metabolism; Animals; Antigens, CD; Body fat; Cell death; Coenzyme A Ligases - genetics; Coenzyme A Ligases - metabolism; Down-regulation; Ferroptosis; Ferroptosis - genetics; Gene expression; Humanities and Social Sciences; Humans; Injury prevention; Ischemia; Liver; Liver - metabolism; Liver - pathology; Liver Transplantation; Liver transplants; Male; Mass spectrometry; Mass spectroscopy; Mice; Mice, Inbred C57BL; mRNA stability; multidisciplinary; Nicotinamide; Pathogenesis; Phenotypes; Receptors, Transferrin - genetics; Receptors, Transferrin - metabolism; Reperfusion; Reperfusion Injury - genetics; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; RNA Stability - genetics; Science; Science (multidisciplinary); Stability; Transferrin; Transplantation; Up-Regulation

Older livers are more prone to hepatic ischaemia/reperfusion injury (HIRI), which severely limits their utilization in liver transplantation. The potential mechanism remains unclear. Here, we demonstrate older livers exhibit increased ferroptosis during HIRI. Inhibiting ferroptosis significantly att...