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. 2019 Apr;26(4):281-288.
doi: 10.1038/s41594-019-0203-4. Epub 2019 Mar 25.

Atg2 mediates direct lipid transfer between membranes for autophagosome formation

Takuo Osawa  1 , Tetsuya Kotani  2 , Tatsuya Kawaoka  3 , Eri Hirata  3 , Kuninori Suzuki  3   4   5 , Hitoshi Nakatogawa  2 , Yoshinori Ohsumi  6 , Nobuo N Noda  7
Affiliations

Atg2 mediates direct lipid transfer between membranes for autophagosome formation

Takuo Osawa et al. Nat Struct Mol Biol. 2019 Apr.

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.

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References

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