Autophagosomes form at ER-mitochondria contact sites

被引：1369

作者：

Hamasaki, Maho ^{[1
,2
]}

Furuta, Nobumichi ^{[3
]}

Matsuda, Atsushi ^{[4
,5
]}

Nezu, Akiko ^{[1
,2
]}

Yamamoto, Akitsugu ^{[6
]}

Fujita, Naonobu ^{[1
,2
]}

Oomori, Hiroko ^{[7
]}

Noda, Takeshi ^{[1
,2
]}

Haraguchi, Tokuko ^{[4
,5
]}

Hiraoka, Yasushi ^{[4
,5
]}

Amano, Atsuo ^{[3
,8
]}

Yoshimori, Tamotsu ^{[1
,2
]}

机构：

[1] Osaka Univ, Grad Sch Med, Dept Genet, Suita, Osaka 5650871, Japan

[2] Osaka Univ, Grad Sch Frontier Biosci, Lab Intracellular Membrane Dynam, Suita, Osaka 5650871, Japan

[3] Osaka Univ, Grad Sch Dent, Ctr Oral Frontier Sci, Dept Oral Frontier Biol, Suita, Osaka 5650871, Japan

[4] Natl Inst Informat & Commun Technol, Nishi Ku, Kobe, Hyogo 6512492, Japan

[5] Osaka Univ, Grad Sch Frontier Biosci, Nucl Dynam Grp, Suita, Osaka 5650871, Japan

[6] Nagahama Inst Biosci & Technol, Fac Biosci, Dept Cell Biol, Nagahama, Shiga 5260829, Japan

[7] Osaka Univ, Res Inst Microbial Dis, Suita, Osaka 5650871, Japan

[8] Osaka Univ, Grad Sch Dent, Dept Prevent Dent, Suita, Osaka 5650871, Japan

来源：

NATURE | 2013年 / 495卷 / 7441期

关键词：

ENDOPLASMIC-RETICULUM; MEMBRANE; LC3; DISSECTION; PROTEINS; ATG14L; CELLS;

D O I：

10.1038/nature11910

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Autophagy is a tightly regulated intracellular bulk degradation/recycling system that has fundamental roles in cellular homeostasis(1). Autophagy is initiated by isolation membranes, which form and elongate as they engulf portions of the cytoplasm and organelles. Eventually isolation membranes dose to form double membrane-bound autophagosomes and fuse with lysosomes to degrade their contents. The physiological role of autophagy has been determined since its discovery, but the origin of autophagosomal membranes has remained unclear. At present, there is much controversy about the organelle from which the membranes originate-the endoplasmic reticulum (ER), mitochondria and plasma membrane(1,2). Here we show that autophagosomes form at the ER-mitochondria contact site in mammalian cells. Imaging data reveal that the pre-autophagosome/autophagosome marker ATG14 (also known as ATG14L) relocalizes to the ER-mitochondria contact site after starvation, and the autophagosome-formation marker ATG5 also localizes at the site until formation is complete. Subcellular fractionation showed that ATG14 co-fractionates in the mitochondria-associated ER membrane(3-5) fraction under starvation conditions. Disruption of the ER-mitochondria contact site prevents the formation of ATG14 puncta. The ER-resident SNARE protein syntaxin 17 (STX17) binds ATG14 and recruits it to the ER-mitochondria contact site. These results provide new insight into organelle biogenesis by demonstrating that the ER-mitochondria contact site is important in autophagosome formation.

引用

页码：389 / 393

页数：5

共 26 条

[1] Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum [J].