RRC ID |
55033
|
Author |
Osawa T, Kotani T, Kawaoka T, Hirata E, Suzuki K, Nakatogawa H, Ohsumi Y, Noda NN.
|
Title |
Atg2 mediates direct lipid transfer between membranes for autophagosome formation.
|
Journal |
Nat Struct Mol Biol
|
Abstract |
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.
|
Volume |
26(4)
|
Pages |
281-288
|
Published |
2019-4-1
|
DOI |
10.1038/s41594-019-0203-4
|
PII |
10.1038/s41594-019-0203-4
|
PMID |
30911189
|
MeSH |
Autophagosomes / metabolism*
Autophagy / physiology
Autophagy-Related Proteins / metabolism
Carrier Proteins / metabolism
Endoplasmic Reticulum / metabolism*
Hydrophobic and Hydrophilic Interactions
Liposomes / metabolism
Phospholipids / metabolism
Schizosaccharomyces / metabolism*
|
IF |
12.109
|
Times Cited |
46
|
Resource |
DNA material |
S. pombe entry clone SpFFH31A11 (SPW052411) |