Mesenchymal stem cell attenuates spinal cord injury by inhibiting mitochondrial quality control-associated neuronal ferroptosis.
Mesenchymal stem cell attenuates spinal cord injury by inhibiting mitochondrial quality control-associated neuronal ferroptosis.
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DOI：
10.1016/j.redox.2023.102871
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发表时间：
2023-11
期刊：
影响因子：
11.4
通讯作者：
Rong, Limin
中科院分区：
文献类型：
--
作者：
Yao, Senyu;Pang, Mao;Wang, Yanheng;Wang, Xiaokang;Lin, Yaobang;Lv, Yanyan;Xie, Ziqi;Hou, Jianfeng;Du, Cong;Qiu, Yuan;Guan, Yuanjun;Liu, Bin;Wang, Jiancheng;Xiang, Andy Peng;Rong, Limin
关键词：
铁凋亡是一种新发现的铁依赖性氧化性细胞死亡形式，并导致脊髓损伤（SCI）中神经元的丢失。线粒体损伤是神经元死亡的重要因素，而线粒体质量控制（MQC）是维持线粒体稳态以促进神经元存活的重要过程。然而，MQC在神经元铁凋亡中的作用尚未明确阐明。在这里，我们进一步证明，神经元主要遭受单细胞RNA测序水平的脊髓损伤中的铁凋亡。从机制上讲，无序的MQC通过过度的线粒体分裂和线粒体自噬来加重铁凋亡。此外，间充质干细胞（MSCs）介导的线粒体转移恢复神经元线粒体池，并通过细胞间隧道纳米管通过线粒体融合抑制铁凋亡。总的来说，这些结果不仅表明，神经元铁凋亡的调节在MQC依赖性的方式，但也实现了MSC衰减神经元铁凋亡在亚细胞器水平的分子机制。更重要的是，它提供了一个有前途的临床翻译策略的基础上干细胞介导的线粒体治疗相关的中枢神经系统疾病。
Ferroptosis is a newly discovered form of iron-dependent oxidative cell death and drives the loss of neurons in spinal cord injury (SCI). Mitochondrial damage is a critical contributor to neuronal death, while mitochondrial quality control (MQC) is an essential process for maintaining mitochondrial homeostasis to promote neuronal survival. However, the role of MQC in neuronal ferroptosis has not been clearly elucidated. Here, we further demonstrate that neurons primarily suffer from ferroptosis in SCI at the single-cell RNA sequencing level. Mechanistically, disordered MQC aggravates ferroptosis through excessive mitochondrial fission and mitophagy. Furthermore, mesenchymal stem cells (MSCs)-mediated mitochondrial transfer restores neuronal mitochondria pool and inhibits ferroptosis through mitochondrial fusion by intercellular tunneling nanotubes. Collectively, these results not only suggest that neuronal ferroptosis is regulated in an MQC-dependent manner, but also fulfill the molecular mechanism by which MSCs attenuate neuronal ferroptosis at the subcellular organelle level. More importantly, it provides a promising clinical translation strategy based on stem cell-mediated mitochondrial therapy for mitochondria-related central nervous system disorders.
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影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
脊髓损伤胶质疤痕反应中分子表达模式和细胞间相互作用的时空动态
影响因子：
5.6
作者：
Gong, Leilei;Gu, Yun;Han, Xiaoxiao;Luan, Chengcheng;Liu, Chang;Wang, Xinghui;Sun, Yufeng;Zheng, Mengru;Fang, Mengya;Yang, Shuhai;Xu, Lai;Sun, Hualin;Yu, Bin;Gu, Xiaosong;Zhou, Songlin
通讯作者：
Zhou, Songlin
脊髓损伤：病理生理学，多分子相互作用和潜在的恢复机制。
影响因子：
5.6
作者：
Anjum A;Yazid MD;Fauzi Daud M;Idris J;Ng AMH;Selvi Naicker A;Ismail OHR;Athi Kumar RK;Lokanathan Y
通讯作者：
Lokanathan Y
影响因子：
82.9
作者：
Breckwoldt, Michael;Pfister, Franz M. J.;Misgeld, Thomas
通讯作者：
Misgeld, Thomas
影响因子：
5.2
作者：
Gong, Fangyi;Ge, Ting;Liu, Jing;Xiao, Jin;Wu, Xiaochuan;Wang, Hehui;Zhu, Yingchun;Xia, Dongdong;Hu, Baiwen
通讯作者：
Hu, Baiwen