Involvement of ferroptosis in metabolic dysfunction-associated steatohepatitis-related liver diseases

Metabolic dysfunction-associated steatotic liver disease (MASLD), as a metabolic liver disease, is emerging as the most prevalent chronic liver disease worldwide. Metabolic dysfunction-associated steatohepatitis (MASH) is the severe form of MASLD, which progresses from simple steatosis to an inflammatory state, even fibrosis and hepatocellular carcinoma. Accumulating evidence has proved that cell death is a hallmark of MASH, while the specific pathogenesis remains unclear. Several cell deaths, including apoptosis, necroptosis, autophagy, and pyroptosis, have been studied in MASLD/MASH. In recent years, ferroptosis, a novel iron-dependent non-apoptotic form of cell death characterized by the excessive accumulation of intracellular iron and lipid peroxidation, has emerged as a promising target in MASLD/MASH. In this review, we mainly summarize the mechanism of ferroptosis and describe the role of ferroptosis in the progression of MASLD to MASH and related diseases, including liver fibrosis and hepatocellular carcinoma. Then, we discussed the crosstalk between ferroptosis and other cell deaths in MASLD/MASH. Finally, we focus on the potential therapeutic applications of targeting ferroptosis in MASH, which might shed light on the future directions of MASH treatment.