Neuronal Mitochondrial Dysfunction Activates the Integrated Stress Response to Induce Fibroblast Growth Factor 21.
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Authors
Restelli, Lisa Michelle
Oettinghaus, Björn
Halliday, Mark
Agca, Cavit
Licci, Maria
Sironi, Lara
Savoia, Claudia
Hench, Jürgen
Tolnay, Markus
Neutzner, Albert
Schmidt, Alexander
Eckert, Anne
Scorrano, Luca
Frank, Stephan
Publication Date
2018-08-07Journal Title
Cell Rep
ISSN
2211-1247
Publisher
Elsevier BV
Volume
24
Issue
6
Pages
1407-1414
Language
eng
Type
Article
Physical Medium
Print
Metadata
Show full item recordCitation
Restelli, L. M., Oettinghaus, B., Halliday, M., Agca, C., Licci, M., Sironi, L., Savoia, C., et al. (2018). Neuronal Mitochondrial Dysfunction Activates the Integrated Stress Response to Induce Fibroblast Growth Factor 21.. Cell Rep, 24 (6), 1407-1414. https://doi.org/10.1016/j.celrep.2018.07.023
Abstract
Stress adaptation is essential for neuronal health. While the fundamental role of mitochondria in neuronal development has been demonstrated, it is still not clear how adult neurons respond to alterations in mitochondrial function and how neurons sense, signal, and respond to dysfunction of mitochondria and their interacting organelles. Here, we show that neuron-specific, inducible in vivo ablation of the mitochondrial fission protein Drp1 causes ER stress, resulting in activation of the integrated stress response to culminate in neuronal expression of the cytokine Fgf21. Neuron-derived Fgf21 induction occurs also in murine models of tauopathy and prion disease, highlighting the potential of this cytokine as an early biomarker for latent neurodegenerative conditions.
Keywords
Alzheimer’s disease, autophagy, biomarker, endoplasmic reticulum, heme, metabolism, mitochondria, neurodegeneration, tau, unfolded protein response, Animals, Fibroblast Growth Factors, Mice, Mitochondria, Neurons
Sponsorship
European Research Council (647479)
Identifiers
External DOI: https://doi.org/10.1016/j.celrep.2018.07.023
This record's URL: https://www.repository.cam.ac.uk/handle/1810/285015
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International
Licence URL: https://creativecommons.org/licenses/by-nc-nd/4.0/
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