Sonic hedgehog pathway activation increases mitochondrial abundance and activity in hippocampal neurons

作者：Pamela J. Yao, Uri Manor, Ronald S. Petralia, Rebecca Deering Brose, Ryan T.Y. Wu, Carolyn M. Ott, Yaxian Wang, Ari Charnoff, Jennifer Lippincott‐Schwartz, Mark P. Mattson · 发表于：Molecular Biology of the Cell · 年份：2016 · DOI：10.1091/mbc.e16-07-0553 · 被引用次数：50 · 研究领域：Hedgehog Signaling Pathway Studies、Epigenetics and DNA Methylation、Genetics and Neurodevelopmental Disorders

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.