The Emerging Role of Ferroptosis in Sepsis.

Abstract

Ferroptosis is a novel form of cell death characterized by the iron-dependent accumulation of lipid peroxides and is different from other types of cell death. The mechanisms of ferroptosis are discussed in the review, including System Xc-, Glutathione Peroxidase 4 pathway, Ferroptosis Suppressor Protein 1 and Dihydroorotate Dehydrogenase pathway. Ferroptosis is associated with the occurrence of various diseases, including sepsis. Research in recent years has displayed that ferroptosis is involved in sepsis occurrence and development. Iron chelators can inhibit the development of sepsis and improve the survival rate of septic mice. The ferroptotic cells can release damage-associated molecular patterns and lipid peroxidation, which further mediate inflammatory responses. Ferroptosis inhibitors can resist sepsis-induced multiple organ dysfunction and inflammation. Finally, we reviewed ferroptosis, an iron-dependent form of cell death that is different from other types of cell death in biochemistry, morphology, and major regulatory mechanisms, which is involved in multiple organ injuries caused by sepsis. Exploring the relationship between sepsis and ferroptosis may yield new treatment targets for sepsis.