Yang Zhifen, Huang Ju, Geng Jiefei, Nair Usha, Klionsky Daniel J
Life Sciences Institute, Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Mol Biol Cell. 2006 Dec;17(12):5094-104. doi: 10.1091/mbc.e06-06-0479. Epub 2006 Oct 4.
In response to stress conditions (such as nutrient limitation or accumulation of damaged organelles) and certain pathological situations, eukaryotic cells use autophagy as a survival mechanism. During nutrient stress the main purpose of autophagy is to degrade cytoplasmic materials within the lysosome/vacuole lumen and generate an internal nutrient pool that is recycled back to the cytosol. This study elucidates a molecular mechanism for linking the degradative and recycling roles of autophagy. We show that in contrast to published studies, Atg22 is not directly required for the breakdown of autophagic bodies within the lysosome/vacuole. Instead, we demonstrate that Atg22, Avt3, and Avt4 are partially redundant vacuolar effluxers, which mediate the efflux of leucine and other amino acids resulting from autophagic degradation. The release of autophagic amino acids allows the maintenance of protein synthesis and viability during nitrogen starvation. We propose a "recycling" model that includes the efflux of macromolecules from the lysosome/vacuole as the final step of autophagy.
作为对压力条件（如营养限制或受损细胞器的积累）以及某些病理情况的响应，真核细胞利用自噬作为一种生存机制。在营养应激期间，自噬的主要目的是在溶酶体/液泡腔内降解细胞质物质，并生成一个内部营养池，该营养池会被循环回到细胞质中。这项研究阐明了一种将自噬的降解和循环作用联系起来的分子机制。我们发现，与已发表的研究不同，Atg22并非溶酶体/液泡内自噬体分解所直接必需的。相反，我们证明Atg22、Avt3和Avt4是部分冗余的液泡外排蛋白，它们介导自噬降解产生的亮氨酸和其他氨基酸的外排。自噬氨基酸的释放使得在氮饥饿期间能够维持蛋白质合成和细胞活力。我们提出了一个“循环”模型，该模型将大分子从溶酶体/液泡的外排作为自噬的最后一步。
