Changaei Mostafa, Azimzadeh Tabrizi Zahra, Karimi Mozhdeh, Kashfi Seyed Adnan, Koochaki Chahardeh Tina, Hashemi Seyed Mahmoud, Soudi Sara
Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Department of Basic Sciences, Biology and Health, Faculty of Interdisciplinary Sciences and Technologies, Tarbiat Modares University, Tehran, Iran.
Cell Commun Signal. 2025 May 20;23(1):232. doi: 10.1186/s12964-025-02237-5.
Mitochondria are traditionally known as the cells' powerhouses; however, their roles go far beyond energy suppliers. They are involved in intracellular signaling and thus play a crucial role in shaping cells' destiny and functionality, including immune cells. Mitochondria can be actively exchanged between immune and non-immune cells via mechanisms such as nanotubes and extracellular vesicles. The mitochondria transfer from immune cells to different cells is associated with physiological and pathological processes, including inflammatory disorders, cardiovascular diseases, diabetes, and cancer. On the other hand, mitochondrial transfer from mesenchymal stem cells, bone marrow-derived stem cells, and adipocytes to immune cells significantly affects their functions. Mitochondrial transfer can prevent exhaustion/senescence in immune cells through intracellular signaling pathways and metabolic reprogramming. Thus, it is emerging as a promising therapeutic strategy for immune system diseases, especially those involving inflammation and autoimmune components. Transferring healthy mitochondria into damaged or dysfunctional cells can restore mitochondrial function, which is crucial for cellular energy production, immune regulation, and inflammation control. Also, mitochondrial transfer may enhance the potential of current therapeutic immune cell-based therapies such as CAR-T cell therapy.
线粒体传统上被认为是细胞的“动力源”；然而，它们的作用远不止于能量供应者。它们参与细胞内信号传导，因此在塑造细胞命运和功能（包括免疫细胞）方面发挥着关键作用。线粒体可以通过纳米管和细胞外囊泡等机制在免疫细胞和非免疫细胞之间进行活跃交换。线粒体从免疫细胞转移到不同细胞与生理和病理过程相关，包括炎症性疾病、心血管疾病、糖尿病和癌症。另一方面，间充质干细胞、骨髓来源的干细胞和脂肪细胞的线粒体转移到免疫细胞会显著影响其功能。线粒体转移可通过细胞内信号通路和代谢重编程防止免疫细胞耗竭/衰老。因此，它正成为一种有前景的免疫系统疾病治疗策略，尤其是那些涉及炎症和自身免疫成分的疾病。将健康的线粒体转移到受损或功能失调的细胞中可以恢复线粒体功能，这对细胞能量产生、免疫调节和炎症控制至关重要。此外，线粒体转移可能会增强当前基于免疫细胞的治疗方法（如嵌合抗原受体T细胞疗法）的潜力。
