Hepatic ischemia–reperfusion injury (HIRI) is a significant clinical challenge in the field of liver surgery and transplantation, and its pathological mechanisms are complex. In recent years, ferroptosis, a novel form of iron-dependent programmed cell death, plays a central role in this injury process. G protein-coupled receptors (GPCRs), as the largest family of membrane receptors in the body, regulate cellular stress and death through extensive signaling networks. This review elucidates the specific molecular mechanisms by which GPCRs regulate ferroptosis in HIRI by affecting key pathways such as lipid peroxidation, iron metabolism homeostasis, and antioxidant defense. It further explores potential therapeutic strategies targeting specific GPCRs to modulate ferroptosis, thereby alleviating liver injury and improving postoperative outcomes, to provide new insights and a theoretical basis for clinical translation.
Hu et al. (2026) studied this question.