Back

Reversible One-way Lipid Transfer at ER-Autophagosome Membrane Contact Sites via Atg2

Hao, L.; Midorikawa, T.; Ogasawara, Y.; Tsuji, T.; Kishimoto, T.; Hama, Y.; Lang, H.; Noda, N. N.; Suzuki, K.

2025-12-11 cell biology
10.1101/2025.03.27.645728 bioRxiv
Show abstract

Bridge-like lipid transfer proteins (LTPs) contain a repeating {beta}-groove domain and long hydrophobic grooves that act as bridges at membrane contact sites (MCSs) to efficiently transfer lipids. Atg2 is one such bridge-like LTP essential for autophagosome formation, during which a newly synthesized isolation membrane (IM) emerges and expands through lipid supply. However, studies on Atg2-mediated lipid transfer are limited to in vitro studies due to the lack of a suitable probe for monitoring phospholipid dynamics in vivo. Here, we characterized the lipophilic dye octadecyl rhodamine B (R18), which internalizes and labels the endoplasmic reticulum (ER) in a manner that requires flippases and oxysterol-binding protein-related proteins. Using R18, we demonstrated phospholipid transfer from the ER to the IM during autophagy in vivo. Upon autophagy termination, we observed reversible phospholipid flow from the IM to the ER in response to environmental changes. Our findings highlight the critical role of bridge-like LTPs in MCS-mediated phospholipid homeostasis.

Published in Journal of Cell Biology (predicted rank #1) · training set

Matching journals

The top 4 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.