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

Pamela J. Yao, Uri Manor, Ronald S. Petralia, Rebecca D. Brose, Ryan T Y Wu, Carolyn Ott, Ya Xian Wang, Ari Charnoff, Jennifer Lippincott-Schwartz, Mark P. Mattson, Erika Holzbaur

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)387-395
Number of pages9
JournalMolecular Biology of the Cell
Issue number3
StatePublished - Feb 1 2017

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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