Mitocytosis, a migrasome-mediated mitochondrial quality-control process

Mitocytosis, a migrasome-mediated mitochondrial quality-control process
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有丝分裂,迁移体介导的线粒体质量控制过程

DOI:
10.1016/j.cell.2021.04.027
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发表时间:
2021-05-27
期刊:
影响因子:
64.5
通讯作者:
Hu, Xiaoyu
Hu, Xiaoyu
中科院分区:
生物学1区
文献类型:
--
作者:
Jiao, Haifeng;Jiang, Dong;Hu, Xiaoyu

文献摘要

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需要清除受损的线粒体以保持线粒体库的质量。在这里,我们报告有丝分裂,一个移行体介导的线粒体质量控制过程。我们发现,在暴露于轻度线粒体应激时,受损的线粒体被转运到迁移体中,随后从迁移细胞中被处理掉。从机制上讲,有丝分裂需要将受损的线粒体定位在细胞外周,这是因为受损的线粒体避免与向内的运动蛋白结合。在功能上,有丝分裂在维持线粒体质量中起重要作用。增强的有丝分裂作用保护细胞免受线粒体应激物诱导的线粒体膜电位(MMP)和线粒体呼吸的损失;相反,在正常条件下阻断有丝分裂作用导致MMP和线粒体呼吸的损失。生理上,我们证明,有丝分裂是必需的维持MMP和活力在体内中性粒细胞。我们认为,有丝分裂是迁移细胞中重要的线粒体质量控制过程,它将线粒体稳态与细胞迁移耦合在一起。
Damaged mitochondria need to be cleared to maintain the quality of the mitochondrial pool. Here, we report mitocytosis, a migrasome-mediated mitochondrial quality-control process. We found that, upon exposure to mild mitochondrial stresses, damaged mitochondria are transported into migrasomes and subsequently disposed of from migrating cells. Mechanistically, mitocytosis requires positioning of damaged mitochondria at the cell periphery, which occurs because damaged mitochondria avoid binding to inward motor proteins. Functionally, mitocytosis plays an important role in maintaining mitochondrial quality. Enhanced mitocytosis protects cells from mitochondrial stressor-induced loss of mitochondrial membrane potential (MMP) and mitochondrial respiration; conversely, blocking mitocytosis causes loss of MMP and mitochondrial respiration under normal conditions. Physiologically, we demonstrate that mitocytosis is required for maintaining MMP and viability in neutrophils in vivo. We propose that mitocytosis is an important mitochondrial quality-control process in migrating cells, which couples mitochondrial homeostasis with cell migration.