Mitochondria are dynamic organelles that produce energy and molecular precursors that are essential for myelin synthesis. Unlike in neurons, mitochondria in oligodendrocytes increase intracellular movement in response to glutamatergic activation and are more susceptible to oxidative stress than in astrocytes or microglia. The signaling pathways that regulate these cell type‐specific mitochondrial responses in oligodendrocytes are not understood. Here, we visualized mitochondria migrating through thin cytoplasmic channels crossing myelin basic protein‐positive compacted membranes and localized within paranodal loop cytoplasm. We hypothesized that local extracellular enrichment of netrin‐1 might regulate the recruitment and function of paranodal proteins and organelles, including mitochondria. We identified rapid recruitment of mitochondria and paranodal proteins, including neurofascin 155 (NF155) and the netrin receptor deleted in colorectal carcinoma (DCC), to sites of contact between oligodendrocytes and netrin‐1‐coated microbeads in vitro. We provide evidence that Src‐family kinase activation and Rho‐associated protein kinase (ROCK) inhibition downstream of netrin‐1 induces mitochondrial elongation, hyperpolarization of the mitochondrial inner membrane, and increases glycolysis. Our findings identify a signaling mechanism in oligodendrocytes that is sufficient to locally recruit paranodal proteins and regulate the subcellular localization, morphology, and function of mitochondria.

中文翻译：

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少突胶质细胞中netrin-1调节的线粒体动力学和生物能量学。

线粒体是动态细胞器，可产生对髓磷脂合成至关重要的能量和分子前体。与神经元不同，少突胶质细胞中的线粒体响应谷氨酸能激活而增加细胞内运动，并且比星形胶质细胞或小胶质细胞更容易受到氧化应激的影响。调节少突胶质细胞中这些细胞类型特异性线粒体反应的信号通路尚不清楚。在这里，我们观察到线粒体通过穿过髓鞘碱性蛋白阳性致密膜的薄细胞质通道迁移并定位在结节旁细胞质内。我们假设 netrin-1 的局部细胞外富集可能调节节旁蛋白和细胞器（包括线粒体）的募集和功能。体外。我们提供的证据表明，netrin-1 下游的 Src 家族激酶激活和 Rho 相关蛋白激酶 (ROCK) 抑制诱导线粒体伸长、线粒体内膜超极化并增加糖酵解。我们的研究结果确定了少突胶质细胞中的一种信号机制，该机制足以局部募集结旁蛋白并调节线粒体的亚细胞定位、形态和功能。