OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine, Technische Universität Dresden, D-01307, Dresden, Germany.
Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, D-01307, Dresden, Germany.
Cell Commun Signal. 2019 Nov 8;17(1):144. doi: 10.1186/s12964-019-0472-x.
Intercellular communication is essential for multicellular tissue vitality and homeostasis. We show that healthy cells message protective signals through direct cell-cell connections to adjacent DNA-damaged cells in a microtubule-dependent manner. In DNA-damaged cells, mitochondria restoration is facilitated by fusion with undamaged mitochondria from healthy cells and their DNA damage repair is optimized in presence of healthy cells. Both, mitochondria transfer and intercellular signaling for an enhanced DNA damage response are critically regulated by the activity of the DNA repair protein ataxia telangiectasia mutated (ATM). These healthy-to-damaged prosurvival processes sustain normal tissue integrity and may be exploitable for overcoming resistance to therapy in diseases such as cancer.
细胞间通讯对于多细胞组织的活力和动态平衡至关重要。我们发现健康细胞通过微管依赖性的直接细胞-细胞连接向相邻的 DNA 损伤细胞传递保护信号。在 DNA 损伤细胞中,受损线粒体与健康细胞中的未受损线粒体融合,促进了线粒体的恢复,并且在健康细胞存在的情况下,其 DNA 损伤修复得到了优化。来自健康细胞的线粒体转移和增强 DNA 损伤反应的细胞间信号传递均受到 DNA 修复蛋白共济失调毛细血管扩张突变(ATM)活性的严格调控。这些有利于受损组织的生存过程维持了正常的组织完整性,并且可能可用于克服癌症等疾病中的治疗抵抗。