Reconstitution of autophagosome nucleation defines Atg9 vesicles as seeds for membrane formation

被引：186

作者：

Sawa-Makarska, Justyna ^{[1
]}

Baumann, Verena ^{[1
]}

Coudevylle, Nicolas ^{[1
]}

von Bulow, Soren ^{[2
]}

Nogellova, Veronika ^{[1
]}

Abert, Christine ^{[1
]}

Schuschnig, Martina ^{[1
]}

Graef, Martin ^{[3
,4
]}

Hummer, Gerhard ^{[2
,5
]}

Martens, Sascha ^{[1
]}

机构：

[1] Univ Vienna, Max Perutz Labs, Dept Biochem & Cell Moira, A-1030 Vienna, Austria

[2] Max Planck Inst Biophys, Dept Theoret Biophys, D-60438 Frankfurt, Germany

[3] Max Planck Inst Biol Ageing, D-50931 Cologne, Germany

[4] Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, D-50931 Cologne, Germany

[5] Goethe Univ Frankfurt, Inst Biophys, D-60438 Frankfurt, Germany

来源：

SCIENCE | 2020年 / 369卷 / 6508期

基金：

欧洲研究理事会; 奥地利科学基金会;

关键词：

SELECTIVE AUTOPHAGY; MOLECULAR-DYNAMICS; PHOSPHATIDYLINOSITOL; 3-PHOSPHATE; ENDOPLASMIC-RETICULUM; ATG12-ATG5; CONJUGATE; PROTEIN-STRUCTURE; BINDING-SITES; COMPLEX; YEAST; BIOGENESIS;

D O I：

10.1126/science.aaz7714

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：

Autophagosomes form de novo in a manner that is incompletely understood. Particularly enigmatic are autophagy-related protein 9 (Atg9)-containing vesicles that are required for autophagy machinery assembly but do not supply the bulk of the autophagosomal membrane. In this study, we reconstituted autophagosome nucleation using recombinant components from yeast. We found that Atg9 proteoliposomes first recruited the phosphatidylinositol 3-phosphate kinase complex, followed by Atg21, the Atg2-Atg18 lipid transfer complex, and the E3-like Atg12-Atg5-Atg16 complex, which promoted Atg8 lipidation. Furthermore, we found that Atg2 could transfer lipids for Atg8 lipidation. In selective autophagy, these reactions could potentially be coupled to the cargo via the Atg19-Atg11-Atg9 interactions. We thus propose that Atg9 vesicles form seeds that establish membrane contact sites to initiate lipid transfer from compartments such as the endoplasmic reticulum.

引用

页码：1206 / +

页数：59

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