Liquid‒liquid phase separation: a potentially fundamental mechanism of sepsis

Sepsis is a life-threatening condition characterized by overactivated inflammation and a dysregulated immune response caused by infection. The predominant mechanism underlying the vulnerability and severity of sepsis has not been fully elucidated. Liquid‒liquid phase separation (LLPS) is a recently discovered, powerful mechanism that drives the formation of membraneless organelles and their biological functions. In particular, emerging evidence indicates that multiple core proteins involved in immune responses, inflammatory signalling, and programmed cell death are organized as protein condensates through LLPS. Here, we present an up-to-date review of the hypothesis that LLPS may underlie the fundamental mechanisms of sepsis, with a focus on the immune system response, changes in inflammatory signalling, and programmed cell death, with the goal of advancing our understanding of the pathological mechanisms of sepsis.