小柯机器人

西班牙庞培法布拉大学Pura Muñoz-Cánoves和西班牙国家心血管研究中心(CNIC)José A. Enríquez共同合作近期取得重要工作进展，他们研究发现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。相关研究成果2022年8月22日在线发表于《细胞—干细胞》杂志上。

研究人员表明线粒体动力学对于卫星细胞的再生能力至关重要。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，他们的发现对肌肉减少症的再生疗法有一定的参考意义。

据介绍，骨骼肌再生依赖于常驻静息干细胞（卫星细胞）的正确扩增，这一过程随着年龄的增长而变得低效。

附：英文原文

Title: Mitochondrial dynamics maintain muscle stem cell regenerative competence throughout adult life by regulating metabolism and mitophagy

Author: Xiaotong Hong, Joan Isern, Silvia Campanario, Eusebio Perdiguero, Ignacio Ramírez-Pardo, Jessica Segalés, Pablo Hernansanz-Agustín, Andrea Curtabbi, Oleg Deryagin, Angela Pollán, José A. González-Reyes, José M. Villalba, Marco Sandri, Antonio L. Serrano, José A. Enríquez, Pura Muoz-Cánoves

Issue&Volume: 2022-08-22

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.

DOI: 10.1016/j.stem.2022.07.009

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(22)00304-6

Cell Stem Cell：《细胞—干细胞》，创刊于2007年。隶属于细胞出版社，最新IF：25.269
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