Linking the unfolded protein response to bioactive lipid metabolism and signalling in the cell non-autonomous extracellular communication of ER stress.
Linking the unfolded protein response to bioactive lipid metabolism and signalling in the cell non-autonomous extracellular communication of ER stress.
复制标题
将未折叠蛋白反应与内质网应激的细胞非自主细胞外通讯中的生物活性脂质代谢和信号传导联系起来。
DOI：
10.1002/bies.202300029
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Watt NT
中科院分区：
文献类型：
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作者：
Watt NT
内质网（ER）细胞器是细胞内蛋白质和脂质生物合成的关键部位。ER功能障碍，称为ER应激，可导致ER内的蛋白质增加和细胞死亡;这是一种导致一系列代谢疾病和癌症的病理生理过程。ER应激导致称为未折叠蛋白反应（UPR）的保护性信号级联的激活。然而，慢性UPR激活可最终导致细胞凋亡。新出现的证据表明，经历ER应激和UPR激活的细胞可以释放细胞外信号，这些信号可以在细胞非自主信号传导机制中将UPR激活传播到靶组织。另外，研究已经确定UPR在生物活性信号脂质（包括鞘脂和神经酰胺）的生物合成中起关键调节作用。在这里，我们权衡证据联合收割机结合这些概念，并提出在ER应激期间，UPR激活驱动神经酰胺脂质的生物合成，神经酰胺脂质被输出并作为细胞非自主信号在靶细胞和组织中传播UPR激活。
The endoplasmic reticulum (ER) organelle is the key intracellular site of both protein and lipid biosynthesis. ER dysfunction, termed ER stress, can result in protein accretion within the ER and cell death; a pathophysiological process contributing to a range of metabolic diseases and cancers. ER stress leads to the activation of a protective signalling cascade termed the Unfolded Protein Response (UPR). However, chronic UPR activation can ultimately result in cellular apoptosis. Emerging evidence suggests that cells undergoing ER stress and UPR activation can release extracellular signals that can propagate UPR activation to target tissues in a cell non‐autonomous signalling mechanism. Separately, studies have determined that the UPR plays a key regulatory role in the biosynthesis of bioactive signalling lipids including sphingolipids and ceramides. Here we weigh the evidence to combine these concepts and propose that during ER stress, UPR activation drives the biosynthesis of ceramide lipids, which are exported and function as cell non‐autonomous signals to propagate UPR activation in target cells and tissues.