title: Sonic hedgehog pathway activation increases mitochondrial abundance and activity in hippocampal neurons.
abstract: 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.
authors.affiliation: Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Yao
authors.affiliation: Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Uri
authors.initials: U
authors.lastname: Manor
authors.affiliation: Advanced Imaging Core, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Petralia
authors.affiliation: Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224.
authors.forename: Rebecca D
authors.initials: RD
authors.lastname: Brose
authors.affiliation: Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224.
authors.forename: Ryan T Y
authors.initials: RT
authors.lastname: Wu
authors.affiliation: Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Ott
authors.affiliation: Advanced Imaging Core, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Ya-Xian
authors.initials: YX
authors.lastname: Wang
authors.affiliation: Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Ari
authors.initials: A
authors.lastname: Charnoff
authors.affiliation: Cell Biology and Metabolism Program, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lippincott-Schwartz
authors.affiliation: Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Mattson
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D020558:GTP Phosphohydrolases / Q000378:metabolism; D057809:HEK293 Cells; D053823:Hedgehog Proteins / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism* / Q000502:physiology; D024101:Mitochondrial Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D051381:Rats; D015398:Signal Transduction / Q000502:physiology
chemical_list: D053823:Hedgehog Proteins; D024101:Mitochondrial Proteins; D020558:GTP Phosphohydrolases