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Supplementary Files: Endoscopic and Endoscopically-Assisted Resection of Intraventricular Lesions Using a Neuroendoscopic Ultrasonic Aspirator

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.

Pharmacological inhibition of dynamin-related protein 1 (Drp1) the main mammalian promoter of mitochondrial fission - has emerged as a promising therapeutic target for the treatment of neuronal injuries. Genetic studies, however, have revealed that inhibiting Drp1 during development leads to defects especially in neuronal differentiation. Bypassing this neurodevelopmental impairment, a number of recent studies have genetically ablated Drp1 in different adult neuronal subpopulations. This has led to new insights into the importance of mitochondrial fission in differentiated neurons and has highlighted potentially severe side effects of this new therapeutic strategy.