线粒体动力学通过调节新陈代谢和线粒体自噬来维持整个成年期的肌肉干细胞再生能力

Mitochondrial dynamics maintain muscle stem cell regenerative competence

throughout adult life by regulating metabolism and mitophagy

Keywords：Drp1, OXPHOS, Aging, Metabolism, Mitochondria, Mitochondrial dynamics, Mitophagy, Muscle regeneration, Muscle stem cells, Satellite cells

关键词：Drp1、OXPHOS、衰老、代谢、线粒体、线粒体动力学、线粒体自噬、肌肉再生、肌肉干细胞、卫星细胞

哺乳动物：小鼠

作者：Hong Xiaotong, Isern Joan, Campanario Silvia, Perdiguero Eusebio, Ramirez-Pardo Ignacio, Segales Jessica, Hernansanz-Agustin Pablo, Curtabbi Andrea, Deryagin Oleg, Pollan Agnela, Gonzalez-Reyes Jose A, Villalba Jose M, Sandri Marco, Serrano Antonio L, Enriquez Jose A, Munoz-Canoves Pura
出版期刊：《Cell Stem Cell》（2022）

Abstract：

Skeletal muscle regeneration depends on the correct expansion of resident quiescent stem cells (satellite cells), a process that becomes less efficient with aging. Here, we show that mitochondrial dynamics are essential for the successful regenerative capacity of satellite cells. The loss of mitochondrial fission in satellite cells-due to aging or genetic impairment-deregulates the mitochondrial electron transport chain (ETC), leading to inefficient oxidative phosphorylation (OXPHOS) metabolism and mitophagy and increased oxidative stress. This state results in muscle regenerative failure, which is caused by the reduced proliferation and functional loss of satellite cells. Regenerative functions can be restored in fission-impaired or aged satellite cells by the re-establishment of mitochondrial dynamics (by activating fission or preventing fusion), OXPHOS, or mitophagy. Thus, mitochondrial shape and physical networking controls stem cell regenerative functions by regulating metabolism and proteostasis. As mitochondrial fission occurs less frequently in the satellite cells in older humans, our findings have implications for regeneration therapies in sarcopenia.

文章摘要：

骨骼肌再生依赖于常驻静止干细胞（卫星细胞）的正确扩增，随着年龄的增长，这一过程的效率会降低。在这里，我们表明线粒体动力学对于卫星细胞的成功再生能力至关重要。由于衰老或遗传损伤，卫星细胞中线粒体裂变的丧失会解除对线粒体电子传递链 (ETC) 的调节，从而导致低效的氧化磷酸化 (OXPHOS) 代谢和线粒体自噬，并增加氧化应激。这种状态导致肌肉再生失败，这是由卫星细胞的增殖减少和功能丧失引起的。通过重建线粒体动力学（通过激活裂变或阻止融合）、OXPHOS 或线粒体自噬，可以在裂变受损或老化的卫星细胞中恢复再生功能。因此，线粒体形状和物理网络通过调节新陈代谢和蛋白质稳态来控制干细胞再生功能。由于线粒体裂变在老年人的卫星细胞中发生的频率较低，我们的研究结果对肌肉减少症的再生疗法有影响。

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