Metabolic reprogramming in hepatic ischemia-reperfusion injury: crosstalk between mitochondria, lipid metabolism, and ferroptosis.

Hepatic ischemia-reperfusion injury is a clinically important complication of liver surgery, transplantation, and trauma, involving oxidative stress, inflammation, immune signaling, microcirculatory dysfunction, metabolic disturbance, and regulated cell death. This review does not aim to provide an exhaustive overview of all hepatic ischemia-reperfusion injury mechanisms, but instead focuses on metabolic reprogramming as an integrative framework linking mitochondrial dysfunction, lipid metabolic remodeling, and ferroptosis. During ischemia, oxygen deprivation and adenosine triphosphate depletion may suppress CPT1A-related fatty acid oxidation, promoting lipid accumulation and metabolic stress. During reperfusion, mitochondrial reactive oxygen species generation, Ca2+ dysregulation, and mitochondrial quality-control imbalance may interact with phospholipid remodeling to increase lipid peroxidation susceptibility. Ferroptosis is discussed as a regulated process driven not only by iron overload, but also by impaired GPX4-dependent lipid peroxide detoxification and dysregulated antioxidant pathways such as the Nrf2/SLC7A11/HO-1 axis. The key message of this review is that hepatic ischemia-reperfusion injury progression may reflect a context-dependent mitochondria-lipid metabolism-ferroptosis network rather than isolated or linear injury pathways. This framework may help identify shared therapeutic nodes while recognizing that several mechanisms remain model-dependent and require further validation.