Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Autophagy. 2022 Aug;18(8):2003-2005. doi: 10.1080/15548627.2022.2056865. Epub 2022 Mar 29.
Neurons depend on macroautophagy/autophagy to maintain cellular homeostasis, and loss of autophagy leads to neurodegeneration. To better understand the role of basal autophagy in neurons, we enriched autophagic vesicles from healthy adult mouse brain and performed mass spectrometry to identify cargos cleared by autophagy. We found that synaptic and mitochondrial proteins comprise nearly half of the unique AV cargos identified in brain. Similarly, synaptic and mitochondrial proteins are major cargos for basal autophagy in neurons. Strikingly, we noted a specific enrichment of mitochondrial nucleoids within neuronal autophagosomes, which occurs through a mechanism distinct from damage-associated mitophagy. Here, we discuss the implications of these findings for our understanding of homeostatic mechanisms in neurons and how the age-dependent decline of autophagy in neurons may contribute to the onset or progression of neurodegenerative disease.
神经元依赖巨自噬/自噬来维持细胞内稳态，而自噬的缺失会导致神经退行性病变。为了更好地理解基础自噬在神经元中的作用，我们从健康成年小鼠脑中富集自噬小体，并进行质谱分析以鉴定被自噬清除的货物。我们发现，突触和线粒体蛋白几乎占大脑中鉴定出的独特自噬小体货物的一半。同样，突触和线粒体蛋白是神经元基础自噬的主要货物。引人注目的是，我们注意到线粒体类核在神经元自噬体中有特异性富集，其发生机制不同于与损伤相关的线粒体自噬。在这里，我们讨论了这些发现对我们理解神经元内稳态机制的意义，以及神经元中自噬随年龄的下降如何导致神经退行性疾病的发生或进展。
