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

Autor:	Yao PJ; Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224., Manor U; Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892., Petralia RS; Advanced Imaging Core, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892., Brose RD; Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224., Wu RT; Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224., Ott C; Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892., Wang YX; Advanced Imaging Core, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892., Charnoff A; Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892., Lippincott-Schwartz J; Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892., Mattson MP; Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224.
Jazyk:	angličtina
Zdroj:	Molecular biology of the cell [Mol Biol Cell] 2017 Feb 01; Vol. 28 (3), pp. 387-395. Date of Electronic Publication: 2016 Dec 08.
DOI:	10.1091/mbc.E16-07-0553
Abstrakt:	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. (© 2017 Yao et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).)
Databáze:	MEDLINE
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