Reggiori Fulvio, Monastyrska Iryna, Shintani Takahiro, Klionsky Daniel J
Life Sciences Institute and Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Mol Biol Cell. 2005 Dec;16(12):5843-56. doi: 10.1091/mbc.e05-07-0629. Epub 2005 Oct 12.
Autophagy is a catabolic multitask transport route that takes place in all eukaryotic cells. During starvation, cytoplasmic components are randomly sequestered into huge double-membrane vesicles called autophagosomes and delivered into the lysosome/vacuole where they are destroyed. Cells are able to modulate autophagy in response to their needs, and under certain circumstances, cargoes such as aberrant protein aggregates, organelles and bacteria can be selectively and exclusively incorporated into autophagosomes. In the yeast Saccharomyces cerevisiae, for example, double-membrane vesicles are used to transport the Ape1 protease into the vacuole, or for the elimination of superfluous peroxisomes. In the present study we reveal that in this organism, actin plays a role in these two types of selective autophagy but not in the nonselective, bulk process. In particular, we show that precursor Ape1 is not correctly recruited to the PAS, the putative site of double-membrane vesicle biogenesis, and superfluous peroxisomes are not degraded in a conditional actin mutant. These phenomena correlate with a defect in Atg9 trafficking from the mitochondria to the PAS.
自噬是一种在所有真核细胞中发生的分解代谢多任务运输途径。在饥饿期间，细胞质成分被随机隔离到称为自噬体的巨大双膜囊泡中，并被输送到溶酶体/液泡中，在那里它们被分解。细胞能够根据自身需要调节自噬，在某些情况下，异常蛋白质聚集体、细胞器和细菌等货物可以被选择性地、专门地纳入自噬体。例如，在酿酒酵母中，双膜囊泡用于将Ape1蛋白酶运输到液泡中，或用于消除多余的过氧化物酶体。在本研究中，我们揭示在这种生物体中，肌动蛋白在这两种类型的选择性自噬中起作用，但在非选择性的大量过程中不起作用。特别是，我们表明前体Ape1没有正确募集到PAS（双膜囊泡生物发生的假定位点），并且在条件性肌动蛋白突变体中多余的过氧化物酶体没有被降解。这些现象与Atg9从线粒体运输到PAS的缺陷相关。
