Reggiori Fulvio, Shintani Takahiro, Nair Usha, Klionsky Daniel J
University of Michigan, Life Sciences Institute, Departments of Molecular, Cellular and Developmental Biology and of Biological Chemistry, Ann Arbor, Michigan, USA.
Autophagy. 2005 Jul;1(2):101-9. doi: 10.4161/auto.1.2.1840. Epub 2005 Jul 11.
Autophagy is a degradative process conserved among eukaryotic cells. It allows the elimination of cytoplasm including aberrant protein aggregates and damaged organelles. Accordingly, it is implicated in normal developmental processes and also serves a protective role in tumor suppression and elimination of invading pathogens, whereas defects in autophagy are associated with various human diseases including cancer and neurodegeneration. Atg proteins mediate the sequestration event that occurs at the preautophagosomal structure (PAS) by catalyzing the formation of double-membrane vesicles, termed autophagosomes. In Saccharomyces cerevisiae, the integral membrane protein Atg9 that is required for autophagy cycles through the PAS. Here, we demonstrate that Atg9 shuttles between this location and mitochondria. These data support a new model where mitochondria may provide at least part of the autophagosomal lipids and suggest a novel cellular function for this well-studied organelle.
自噬是真核细胞中保守的降解过程。它允许清除包括异常蛋白质聚集体和受损细胞器在内的细胞质。因此,它参与正常发育过程,并且在肿瘤抑制和清除入侵病原体方面发挥保护作用,而自噬缺陷与包括癌症和神经退行性疾病在内的各种人类疾病相关。自噬相关蛋白(Atg蛋白)通过催化形成称为自噬体的双膜囊泡,介导在自噬前体结构(PAS)发生的隔离事件。在酿酒酵母中,自噬所需的整合膜蛋白Atg9通过PAS进行循环。在这里,我们证明Atg9在该位置和线粒体之间穿梭。这些数据支持了一个新模型,即线粒体可能至少提供部分自噬体脂质,并为这个经过充分研究的细胞器提出了一种新的细胞功能。