TY - JOUR
T1 - Atg2 mediates direct lipid transfer between membranes for autophagosome formation
AU - Osawa, Takuo
AU - Kotani, Tetsuya
AU - Kawaoka, Tatsuya
AU - Hirata, Eri
AU - Suzuki, Kuninori
AU - Nakatogawa, Hitoshi
AU - Ohsumi, Yoshinori
AU - Noda, Nobuo N.
N1 - Funding Information:
We thank Y. Ishii for her help with protein expression, C. Kondo-Kakuta and Y. Kamada (National Institute for Basic Biology, Japan) for generation of the pCK6 plasmid, S. Kawano and T. Endo (Kyoto Sangyo University) for providing the plasmid for the Mmm1–Mdm12 complex, H. Tachikawa (University of Tokyo) for providing the cDNA of Vps13, and A. I. May for proofreading the manuscript. S. pombe Atg2 cDNA was provided by the RIKEN BioResource Research Center (BRC) through the National BioResource Project of the Ministry of Education, Culture, Sports, Science and Technology (MEXT) and Agency for Medical Research and Development (AMED), Japan. The synchrotron radiation experiments were performed using beamlines BL-1A and BL-17A at Photon Factory (KEK, Japan). This work was supported by the Japan Science and Technology Agency (JST) Core Research for Evolutionary Science and Technology (CREST, Grant Number JPMJCR13M7 to N.N.N. and H.N.),
Funding Information:
the Japan Society for the Promotion of Science (JSPS) KAKENHI Grant-in-Aid for Scientific Research 25111004 and 18H03989 (to N.N.N.), 25111003 (to H.N.), 16H06375 (to Y.O.), 18J13429 (to E.H.), 16H06280 and 18H04853 (to K.S.), and the Platform Project for Supporting in Drug Discovery and Life Science Research (Platform for Drug Discovery, Informatics, and Structural Life Science) from MEXT and AMED.
Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2019/4/1
Y1 - 2019/4/1
N2 - A key event in autophagy is autophagosome formation, whereby the newly synthesized isolation membrane (IM) expands to form a complete autophagosome using endomembrane-derived lipids. Atg2 physically links the edge of the expanding IM with the endoplasmic reticulum (ER), a role that is essential for autophagosome formation. However, the molecular function of Atg2 during ER–IM contact remains unclear, as does the mechanism of lipid delivery to the IM. Here we show that the conserved amino-terminal region of Schizosaccharomyces pombe Atg2 includes a lipid-transfer-protein-like hydrophobic cavity that accommodates phospholipid acyl chains. Atg2 bridges highly curved liposomes, thereby facilitating efficient phospholipid transfer in vitro, a function that is inhibited by mutations that impair autophagosome formation in vivo. These results suggest that Atg2 acts as a lipid-transfer protein that supplies phospholipids for autophagosome formation.
AB - A key event in autophagy is autophagosome formation, whereby the newly synthesized isolation membrane (IM) expands to form a complete autophagosome using endomembrane-derived lipids. Atg2 physically links the edge of the expanding IM with the endoplasmic reticulum (ER), a role that is essential for autophagosome formation. However, the molecular function of Atg2 during ER–IM contact remains unclear, as does the mechanism of lipid delivery to the IM. Here we show that the conserved amino-terminal region of Schizosaccharomyces pombe Atg2 includes a lipid-transfer-protein-like hydrophobic cavity that accommodates phospholipid acyl chains. Atg2 bridges highly curved liposomes, thereby facilitating efficient phospholipid transfer in vitro, a function that is inhibited by mutations that impair autophagosome formation in vivo. These results suggest that Atg2 acts as a lipid-transfer protein that supplies phospholipids for autophagosome formation.
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U2 - 10.1038/s41594-019-0203-4
DO - 10.1038/s41594-019-0203-4
M3 - Article
C2 - 30911189
AN - SCOPUS:85063536856
SN - 1545-9993
VL - 26
SP - 281
EP - 288
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
IS - 4
ER -