Division of Neuropathology, Institute of Medical Genetics and Pathology, University Hospital Basel, Basel 4031, Switzerland; University of Basel, Basel 4001, Switzerland.
Division of Neuropathology, Institute of Medical Genetics and Pathology, University Hospital Basel, Basel 4031, Switzerland.
Cell Rep. 2018 Aug 7;24(6):1407-1414. doi: 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.
应激适应对于神经元健康至关重要。虽然已经证明了线粒体在神经元发育中的基本作用，但仍不清楚成年神经元如何对线粒体功能的改变做出反应，以及神经元如何感知、信号传递和对线粒体及其相互作用的细胞器的功能障碍做出反应。在这里，我们表明，线粒体分裂蛋白 Drp1 的神经元特异性、诱导型体内缺失会导致内质网应激，从而激活整合应激反应，最终导致神经元细胞因子 Fgf21 的表达。Fgf21 的诱导也发生在tau 病和朊病毒病的小鼠模型中，突出了这种细胞因子作为潜在神经退行性疾病的早期生物标志物的潜力。
