美国加州大学Andrew Dillin团队近期取得重要工作进展，他们研究提出，细胞外基质（ECM）能够影响线粒体稳态。相关研究成果2024年6月27日在线发表于《细胞》杂志上。
据介绍，细胞内稳态受到来自微环境刺激的复杂影响，包括信号分子、代谢物和病原体。线粒体作为细胞内的信号中枢，整合来自不同细胞内区室的信息，调节细胞信号和代谢。多项研究表明，线粒体可能对各种细胞外信号事件作出反应。然而，尚不清楚ECM的变化如何影响线粒体稳态以调节动物生理。
研究人员发现ECM重塑以演化保守的方式改变线粒体稳态。从机制上讲，ECM重塑触发TGF-β反应，以诱导线粒体分裂和线粒体的未折叠蛋白反应（UPRMT）。从有机体层面上激讲，ECM重塑通过增强线粒体应激反应促进动物防御病原体。研究人员认为，这种ECM-线粒体相互作用代表了一种古老的免疫途径，它检测感染或机械应激诱导的ECM损伤，从而启动适应性线粒体免疫和代谢反应。
附：英文原文
Title: The extracellular matrix integrates mitochondrial homeostasis
Author: Hanlin Zhang, C. Kimberly Tsui, Gilberto Garcia, Larry K. Joe, Haolun Wu, Ayane Maruichi, Wudi Fan, Sentibel Pandovski, Peter H. Yoon, Brant M. Webster, Jenni Durieux, Phillip A. Frankino, Ryo Higuchi-Sanabria, Andrew Dillin
Issue&Volume: 2024-06-27
Abstract: Cellular homeostasis is intricately influenced by stimuli from the microenvironment,including signaling molecules, metabolites, and pathogens. Functioning as a signalinghub within the cell, mitochondria integrate information from various intracellularcompartments to regulate cellular signaling and metabolism. Multiple studies haveshown that mitochondria may respond to various extracellular signaling events. However,it is less clear how changes in the extracellular matrix (ECM) can impact mitochondrialhomeostasis to regulate animal physiology. We find that ECM remodeling alters mitochondrialhomeostasis in an evolutionarily conserved manner. Mechanistically, ECM remodelingtriggers a TGF-β response to induce mitochondrial fission and the unfolded proteinresponse of the mitochondria (UPRMT). At the organismal level, ECM remodeling promotes defense of animals against pathogensthrough enhanced mitochondrial stress responses. We postulate that this ECM-mitochondriacrosstalk represents an ancient immune pathway, which detects infection- or mechanical-stress-inducedECM damage, thereby initiating adaptive mitochondria-based immune and metabolic responses.
DOI: 10.1016/j.cell.2024.05.057
Source: https://www.cell.com/cell/abstract/S0092-8674(24)00638-X