Department of Neuroscience and Department of Cell Biology, Yale University School of Medicine, PO Box 9812, New Haven, CT 06536-0812, USA; Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA.
Department of Neuroscience and Department of Cell Biology, Yale University School of Medicine, PO Box 9812, New Haven, CT 06536-0812, USA; Instituto de Neurobiología José del Castillo, Universidad de Puerto Rico, San Juan, PR, USA.
Neuron. 2020 Mar 18;105(6):961-973. doi: 10.1016/j.neuron.2020.01.018.
Autophagy is a key cellular degradative pathway, important for neuronal homeostasis and function. Disruption of autophagy is associated with neuronal dysfunction and neurodegeneration. Autophagy is compartmentalized in neurons, with specific stages of the pathway occurring in distinct subcellular compartments. Coordination of these stages drives progression of autophagy and enables clearance of substrates. Yet, we are only now learning how these distributed processes are integrated across the neuron. In this review, we focus on the cell biological course of autophagy in neurons, from biogenesis at the synapse to degradation in the soma. We describe how the steps of autophagy are distributed across neuronal subcellular compartments, how local machinery regulates autophagy, and the impact of coordinated regulation on neuronal physiology and disease. We also discuss how recent advances in our understanding of neuronal autophagic mechanisms have reframed how we think about the role of local regulation of autophagy in all tissues.
自噬是一种关键的细胞降解途径，对于神经元的内稳态和功能很重要。自噬的破坏与神经元功能障碍和神经退行性变有关。自噬在神经元中是分隔的，该途径的特定阶段发生在不同的细胞内隔室中。这些阶段的协调驱动自噬的进展，并使底物得以清除。然而，我们现在才开始了解这些分布式过程是如何在神经元中整合的。在这篇综述中，我们专注于神经元中自噬的细胞生物学过程，从突触处的生物发生到胞体中的降解。我们描述了自噬的步骤如何分布在神经元的亚细胞隔室中，局部机制如何调节自噬，以及协调调节对神经元生理学和疾病的影响。我们还讨论了我们对神经元自噬机制的理解的最新进展如何重新定义了我们对自噬的局部调节在所有组织中的作用的看法。
