2013

YOSHIMORI Tamotsu, HAMASAKI Maho ≪Genetics≫ “Autophagosomes form at ER–mitochondria contact sites”

免疫制御学-1

免疫制御学-2
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2013-3-4
PublishNature (2013) doi:10.1038/nature11910

Autophagy is a tightly regulated intracellular bulk degradation/recycling system that plays fundamental roles in cellular homeostasis. Autophagy is initiated by isolation membranes, they then elongate as engulfing portions of the cytoplasm and organelles. Eventually isolation membranes close to form double membrane-bound autophagosomes and fuse with lysosomes to degrade their contents. Even as the physiological role of autophagy has been elucidated since its discovery, the origin of autophagosomal membranes has remained unclear. At present, there is much controversy regarding the organelle from which the membranes originate; the endoplasmic reticulum (ER), mitochondria, and plasma membrane. Here we show that autophagosomes form at the ER-mitochondria contact site. Imaging data reveal that Atg14L (a component of the autophagosome formation machinery) relocalizes to the ER-mitochondria contact site upon starvation and also Atg5 (autophagosome formation marker) localizes at the site until formation complete. Subcellular fractionation revealed Atg14L co-fractionates in the mitochondria-associated ER membrane (MAM) fraction under starvation conditions. Disruption of the ER-mitochondria contact site prevents formation of Atg14L puncta. The ER-resident SNARE protein Syntaxin 17 (Stx17) binds Atg14L and recruits it to the ER-mitochondria contact site. These results provide new insight into organelle biogenesis by demonstrating the ER-mitochondria contact site is important in autophagosome formation.

URLhttp://www.fbs.osaka-u.ac.jp/labs/yoshimori/