Neuronal Mitochondrial Dysfunction Activates the Integrated Stress Response to Induce Fibroblast Growth Factor 21.
Restelli, Lisa Michelle
MetadataShow full item record
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
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.
Neurons, Mitochondria, Animals, Mice, Fibroblast Growth Factors
European Research Council (647479)
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
Attribution-NonCommercial-NoDerivatives 4.0 International
Licence URL: https://creativecommons.org/licenses/by-nc-nd/4.0/