Scinderin promotes fusion of electron transport chain dysfunctional muscle stem cells with myofibers.
Scinderin promotes fusion of electron transport chain dysfunctional muscle stem cells with myofibers.
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DOI：
10.1038/s43587-021-00164-x
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Mishra P
中科院分区：
文献类型：
--
作者：
Wang X;Shelton SD;Bordieanu B;Frank AR;Yi Y;Venigalla SSK;Gu Z;Lenser NP;Glogauer M;Chandel NS;Zhao H;Zhao Z;McFadden DG;Mishra P
肌肉干细胞（MuSCs）经历与年龄相关的数量和功能下降，伴随着线粒体电子传递链（ETC）功能障碍和活性氧（ROS）增加。这些变化的来源以及musc对线粒体功能障碍的反应尚不清楚。我们在这里报道，为了响应线粒体ROS，小鼠MuSCs直接与邻近的肌纤维融合；这种现象将etc -功能失调的musc从干细胞区室中移除。musc -肌纤维融合依赖于Scinderin的诱导，Scinderin促进膜融合所需的肌动蛋白依赖性突起的形成。在衰老过程中，我们发现下降的MuSC种群在线粒体基因组中积累突变，但选择不功能失调的变体。在没有辛德勒清除的情况下，衰老过程中MuSC数量的下降受到抑制；然而，etc -功能失调的musc被保留，并能再生功能失调的肌纤维。我们提出了一种模型，其中etc -功能失调的musc通过与分化组织融合从干细胞区室中移除。
Muscle stem cells (MuSCs) experience age-associated declines in number and function, accompanied by mitochondrial electron transport chain (ETC) dysfunction and increased reactive oxygen species (ROS). The source of these changes, and how MuSCs respond to mitochondrial dysfunction, is unknown. We report here that in response to mitochondrial ROS, murine MuSCs directly fuse with neighboring myofibers; this phenomenon removes ETC-dysfunctional MuSCs from the stem cell compartment. MuSC-myofiber fusion is dependent on the induction of Scinderin, which promotes formation of actin-dependent protrusions required for membrane fusion. During aging, we find that the declining MuSC population accumulates mutations in the mitochondrial genome, but selects against dysfunctional variants. In the absence of clearance by Scinderin, the decline in MuSC numbers during aging is repressed; however, ETC-dysfunctional MuSCs are retained and can regenerate dysfunctional myofibers. We propose a model in which ETC-dysfunctional MuSCs are removed from the stem cell compartment by fusing with differentiated tissue.
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