p53-Dependent ferroptosis pathways in sepsis

Abstract

Sepsis is caused by complex infections, trauma, and major surgery that results in high morbidity and mortality. As one of the leading causes of death in the intensive care unit (ICU）, sepsis causes organ dysfunction and death via a vicious cycle of uncontrolled inflammatory responses and immunosuppression. Ferroptosis is an iron-dependent cellular death pathway driven by the accumulation of lipid peroxides, which occurs in sepsis. p53 is an important regulator of ferroptosis. Under intracellular/extracellular stimulation and pressure, p53 acts as a transcription factor to regulate the expression of downstream genes, which help cells/bodies to resist stimuli. p53 can also function independently as an important mediator. The understanding of key cellular and molecular mechanisms of ferroptosis facilitates the prognosis of sepsis. This article describes the molecular mechanism and role of p53 in sepsis-induced ferroptosis, and introduces some potential therapeutic targets for sepsis-induced ferroptosis, which highlights the dominant and potential therapeutic role of p53 in sepsis. Keywords: p53, acetylation, Sirt3, ferroptosis, sepsis, therapy.