PMID- 35281461 OWN - NLM STAT- MEDLINE DCOM- 20220324 LR - 20220324 IS - 1942-0994 (Electronic) IS - 1942-0900 (Print) IS - 1942-0994 (Linking) VI - 2022 DP - 2022 TI - Tunneling Nanotube-Mediated Mitochondrial Transfer Rescues Nucleus Pulposus Cells from Mitochondrial Dysfunction and Apoptosis. PG - 3613319 LID - 10.1155/2022/3613319 [doi] LID - 3613319 AB - Stem cell-based therapy has been indicated to be beneficial for intervertebral disc regeneration. However, the underlying mechanisms have not been fully identified. The present study showed that bone marrow mesenchymal stem cells (BMSCs) donated mitochondria to adjacent nucleus pulposus cells (NPCs) in a coculture system. The mode of mitochondrial transfer between these cells was intercellular tunneling nanotube (TNT), which acted as a transportation expressway for mitochondria. NPCs acquired additional mitochondria from BMSCs in a concentration-dependent manner after rotenone-induced mitochondrial dysfunction in NPCs. Further research demonstrated that TNT-mediated mitochondrial transfer rescued NPCs from mitochondrial dysfunction and apoptosis, which was indicated by the recovery of the mitochondrial respiratory chain, the increase in mitochondrial membrane potential, and the decreases in reactive oxygen species (ROS) levels and apoptosis rates. Furthermore, Miro1, a critical protein that regulates mitochondrial movement, was knocked down in BMSCs and significantly reduced mitochondrial transfer from BMSCs to NPCs. These results suggested that Miro1 depletion inhibited the rescue of NPCs with mitochondrial dysfunction. Taken together, our data shed light on a novel mechanism by which BMSCs rescue impaired NPCs, providing a concrete foundation to study the critical role of intercellular interactions in disc regeneration. CI - Copyright (c) 2022 Fan Yang et al. FAU - Yang, Fan AU - Yang F AD - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. FAU - Zhang, Yanbin AU - Zhang Y AD - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. FAU - Liu, Sheng AU - Liu S AD - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. FAU - Xiao, Jiheng AU - Xiao J AD - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. FAU - He, Yuxin AU - He Y AD - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. FAU - Shao, Zengwu AU - Shao Z AD - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. FAU - Zhang, Yuhui AU - Zhang Y AD - Britton Chance Center and MoE Key Laboratory for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology, Wuhan 430074, China. FAU - Cai, Xianyi AU - Cai X AUID- ORCID: 0000-0002-8726-2067 AD - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. FAU - Xiong, Liming AU - Xiong L AUID- ORCID: 0000-0002-9003-4671 AD - Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. LA - eng PT - Journal Article DEP - 20220304 PL - United States TA - Oxid Med Cell Longev JT - Oxidative medicine and cellular longevity JID - 101479826 RN - 0 (Tunneling Nanotubes) SB - IM MH - Apoptosis MH - Cell Membrane Structures/*metabolism MH - Cells, Cultured MH - Mesenchymal Stem Cells/*metabolism MH - Mitochondria/*metabolism MH - Nanotubes MH - Nucleus Pulposus/*metabolism PMC - PMC8916857 COIS- The authors declare no conflicts of interest. EDAT- 2022/03/15 06:00 MHDA- 2022/03/25 06:00 PMCR- 2022/03/04 CRDT- 2022/03/14 05:22 PHST- 2021/12/08 00:00 [received] PHST- 2022/01/28 00:00 [revised] PHST- 2022/02/16 00:00 [accepted] PHST- 2022/03/14 05:22 [entrez] PHST- 2022/03/15 06:00 [pubmed] PHST- 2022/03/25 06:00 [medline] PHST- 2022/03/04 00:00 [pmc-release] AID - 10.1155/2022/3613319 [doi] PST - epublish SO - Oxid Med Cell Longev. 2022 Mar 4;2022:3613319. doi: 10.1155/2022/3613319. eCollection 2022.