Sonic hedgehog pathway activation increases mitochondrial abundance and activity in hippocampal neurons.
Sonic hedgehog pathway activation increases mitochondrial abundance and activity in hippocampal neurons.
复制标题
声波刺猬通路激活增加了海马神经元的线粒体丰度和活性。
DOI：
10.1091/mbc.e16-07-0553
复制
发表时间：
2017
影响因子：
3.3
通讯作者：
Mattson,MarkP
中科院分区：
文献类型：
--
作者：
Yao,PamelaJ;Manor,Uri;Petralia,RonaldS;Brose,RebeccaD;Wu,RyanTY;Ott,Carolyn;Wang,Ya-Xian;Charnoff,Ari;Lippincott-Schwartz,Jennifer;Mattson,MarkP
线粒体是重要的细胞器，其生物发生、结构和功能受到许多信号通路的调节。我们提供的证据表明，在海马神经元中，音刺猬 (Shh) 信号通路的激活会影响线粒体的多个方面。经过Shh处理的神经元中线粒体质量显着增加。通过生化和荧光成像分析，我们表明，Shh 信号传导活性至少部分是通过抑制线粒体裂变蛋白动力蛋白样 GTPase Drp1 来减少线粒体裂变并促进线粒体伸长。电子显微镜显示，Shh 处理的神经元的线粒体电子密度更高，并且具有更高的膜电位和呼吸活性。我们进一步表明，Shh 可以保护神经元免受多种应激，包括线粒体毒物鱼藤酮、淀粉样β-肽、过氧化氢和高水平的谷氨酸。总的来说，我们的数据表明 Shh 通路活性与海马神经元线粒体的生理特性之间存在联系。
Mitochondria are essential organelles whose biogenesis, structure, and function are regulated by many signaling pathways. We present evidence that, in hippocampal neurons, activation of the Sonic hedgehog (Shh) signaling pathway affects multiple aspects of mitochondria. Mitochondrial mass was increased significantly in neurons treated with Shh. Using biochemical and fluorescence imaging analyses, we show that Shh signaling activity reduces mitochondrial fission and promotes mitochondrial elongation, at least in part, via suppression of the mitochondrial fission protein dynamin-like GTPase Drp1. Mitochondria from Shh-treated neurons were more electron-dense, as revealed by electron microscopy, and had higher membrane potential and respiratory activity. We further show that Shh protects neurons against a variety of stresses, including the mitochondrial poison rotenone, amyloid β-peptide, hydrogen peroxide, and high levels of glutamate. Collectively our data suggest a link between Shh pathway activity and the physiological properties of mitochondria in hippocampal neurons.