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

Abstract 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...

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Bibliographic Details
Main Authors: Huiyi Chen, Shunyi Huang, Longcheng Quan, Caiyuan Yu, Yang Zhu, Xiaocong Sun, Yuanli Zhang, Liehua Deng, Feng Chen
Format: Article
Language:English
Published: Nature Publishing Group 2025-07-01
Series:Cell Death Discovery
Online Access:https://doi.org/10.1038/s41420-025-02599-2
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Summary:Abstract 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.
ISSN:2058-7716