Damage-associated molecular patterns (DAMPs) are molecules within living cells that are released when cell membranes are ruptured. Although DAMPs have physiological functions inside the cell, once DAMPs are released extracellularly, they elicit various biological responses, including inflammation, proliferation, tissue damage, and tissue repair, in a context-dependent manner. In past decades, it was assumed that the release of DAMPs was induced by a membrane rupture, caused by passive ATP depletion, or by chemical or mechanical damage to the membrane. However, that concept has been challenged by recent advancements in understanding the regulation of cell death. Necroptosis is a form of regulated cell death, where cells show necrotic morphology. Necroptosis is triggered by death receptors, toll-like receptors, and some viral infections. The membrane rupture is executed by the mixed lineage-like kinase domain-like pseudokinase (MLKL), which forms oligomers that translocate to the plasma membrane during necroptosis. Although the causal relationship between MLKL function and membrane rupture has been extensively investigated, the detailed molecular mechanisms by which oligomerized MLKL induces membrane rupture are not fully understood. This review summarizes recent advances in understanding how MLKL regulates DAMP release and new technologies for visualizing DAMP release at single-cell resolution.

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调节坏死细胞释放损伤相关分子模式

损伤相关分子模式 (DAMP) 是活细胞内的分子，当细胞膜破裂时会释放出来。虽然 DAMPs 在细胞内具有生理功能，但一旦 DAMPs 释放到细胞外，它们就会以上下文相关的方式引发各种生物反应，包括炎症、增殖、组织损伤和组织修复。在过去的几十年里，人们认为 DAMP 的释放是由膜破裂引起的，由被动 ATP 耗竭或膜的化学或机械损伤引起。然而，这一概念受到了最近在理解细胞死亡调控方面取得的进展的挑战。坏死性凋亡是一种受调节的细胞死亡形式，其中细胞表现出坏死形态。坏死性凋亡由死亡受体、toll 样受体和一些病毒感染触发。膜破裂由混合谱系样激酶结构域样假激酶 (MLK​​L) 执行，MLKL 在坏死性凋亡过程中形成易位至质膜的寡聚体。尽管 MLKL 功能与膜破裂之间的因果关系已被广泛研究，但寡聚化 MLKL 诱导膜破裂的详细分子机制尚不完全清楚。这篇综述总结了最近在了解 MLKL 如何调节 DAMP 释放方面取得的进展，以及在单细胞分辨率下可视化 DAMP 释放的新技术。低聚 MLKL 诱导膜破裂的详细分子机制尚不完全清楚。这篇综述总结了最近在了解 MLKL 如何调节 DAMP 释放方面取得的进展，以及在单细胞分辨率下可视化 DAMP 释放的新技术。低聚 MLKL 诱导膜破裂的详细分子机制尚不完全清楚。这篇综述总结了最近在了解 MLKL 如何调节 DAMP 释放方面取得的进展，以及在单细胞分辨率下可视化 DAMP 释放的新技术。