细胞之间线粒体转移的主要途径、主要作用及主要调控机制  

Main pathways,roles,and regulatory mechanisms of intercellular mitochondrial transfer

作　　者：李兴福 周光前[1] 陆伟 Li Xingfu;Zhou Guangqian;Lu Wei(Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging,National-Regional Key Technology Engineering Laboratory for Medical Ultrasound,School of Biomedical Engineering,Shenzhen University Medical School,Shenzhen 518060,Guangdong Province,China;Department of Sports Medicine,Shenzhen Second People’s Hospital,Shenzhen 518035,Guangdong Province,China)

机构地区：[1]深圳大学医学部生物医学工程学院,医学超声关键技术国家地方联合工程实验室,广东省生物医学信息检测与超声成像重点实验室,广东省深圳市518060 [2]深圳市第二人民医院运动医学科,广东省深圳市518035

出　　处：《中国组织工程研究》2025年第25期5443-5453,共11页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金面上项目(82072515),项目负责人:陆伟;深圳市科创委基础研究面上项目(JCYJ20220530150615035),项目负责人:李兴福。

摘　　要：背景:线粒体功能障碍导致细胞衰老凋亡,可加重组织损伤。细胞之间线粒体转移促进损伤细胞恢复线粒体功能,有助于治疗线粒体相关疾病。目的:综述细胞之间线粒体转移的作用及调控机制。方法:检索中国知网和PubMed数据库2014-2024年关于细胞之间线粒体转移的文献,以“线粒体转移,隧道纳米管,缝隙连接,微囊泡,细胞融合”为中文检索词,以“Mitochondrial transfer,Tunneling nanotubes,gap junctions,microvesicles,cell fusion”为英文检索词,最终共纳入74篇文献进行分析。结果与结论:①总结了细胞之间线粒体转移的4个主要途径:包括隧道纳米管、缝隙连接、细胞融合和微囊泡。②梳理了细胞之间线粒体转移的主要作用,包括物质交换、信息传递、改善宿主细胞线粒体功能、抑制氧化应激、提高细胞增殖活力及抗炎抗衰老等。③总结了细胞之间线粒体转移的主要调控机制,包括Miro 1促进隧道纳米管形成和线粒体转移、隧道纳米管转移线粒体依赖宿主细胞环状ADP核糖水解酶表达、氧化应激环境诱导隧道纳米管形成、缝隙连接具有Ca^(2+)依赖性、缝隙连接蛋白43影响缝隙连接形成、激活Ras1蛋白和肌动蛋白有助于细胞融合、肌动蛋白和Rab6参与调控线粒体出胞、激活肌动蛋白和NAD+-CD38-cADPR-Ca^(2+)信号通路促进线粒体入胞等。④在细胞信号传导蛋白、细胞动力学相关蛋白及氧化应激环境的影响下,细胞通过隧道纳米管、缝隙连接、微囊泡及细胞融合进行线粒体转移。⑤线粒体转移是细胞之间物质交换和信息交流的重要途径,与疾病的发生发展息息相关,可为治疗线粒体相关疾病提供新的思路,但对细胞间线粒体转移的作用及调控机制仍需进一步探究。BACKGROUND:Mitochondrial dysfunction leads to cellular senescence and apoptosis,exacerbating tissue damage.Intercellular mitochondrial transfer in injured cells restores mitochondrial function,offering potential therapeutic strategies for mitochondria-related diseases.OBJECTIVE:To review the effects and regulatory mechanisms of intercellular mitochondrial transfer.METHODS:A comprehensive literature search was conducted on mitochondrial transfer between cells in the CNKI and PubMed databases from 2014 to 2024.The Chinese and English search terms used were“mitochondrial transfer,tunneling nanotubes,gap junctions,microvesicles,cell fusion.”Eventually,a total of 74 articles were analyzed.RESULTS AND CONCLUSION:(1)The present review provides a comprehensive overview of the four principal mechanisms underlying mitochondrial transfer between cells,encompassing tunneling nanotubes,gap junctions,cell fusion,and microvesicles.(2)This article provides a comprehensive analysis of the pivotal roles played by intercellular mitochondrial transfer,encompassing material exchange,transmission of information,enhancement of host cell mitochondrial function,attenuation of oxidative stress,augmentation of cellular proliferation activity,anti-inflammatory effects,and anti-aging properties.(3)The article provides a comprehensive overview of the main regulatory mechanisms involved in cell mitochondria transfer.These include the promotion of tunneling nanotube formation and mitochondrial transfer by Miro 1,dependence of tunneling nanotubes-mediated mitochondrial transfer on host cell cyclic ADP ribose hydrolase expression,induction of tunneling nanotube formation in an oxidative stress environment,Ca^(2+)-dependent gap junctions,influence of Cx43 on gap junction formation,contribution of Ras1 and actin activation to cell fusion,and involvement of actin and Rab6 in the regulation of mitochondrial exocytosis,activation of actin and NAD+-CD38-cADPR-Ca^(2+)signaling pathways for promoting mitochondrial entry.(4)The transfer of mitochondri

关 键 词：线粒体转移 隧道纳米管 缝隙连接 微囊泡 细胞融合 干细胞 氧化应激 衰老 

分 类 号：R459.9[医药卫生—治疗学] R363[医药卫生—临床医学] R364