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bioRxiv · 10.1101/2020.05.12.090977

Kinetics of Atg2-mediated lipid transfer from the ER can account for phagophore expansion

von Bülow, S.·Hummer, G.
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Abstract

The protein Atg2 has been proposed to form a membrane tether that mediates lipid transfer from the ER to the phagophore in autophagy. However, recent kinetic measurements on the human homolog ATG2A indicated a transport rate of only about one lipid per minute, which would be far too slow to deliver the millions of lipids required to form a phagophore on a physiological time scale. Here, we revisit the analysis of the fluorescence quenching experiments. We develop a detailed kinetic model of the lipid transfer between two membranes bridged by a tether that forms a conduit for lipids. The model provides an excellent fit to the fluorescence experiments, with a lipid transfer rate of about 100 per second and protein. At this rate, Atg2-mediated transfer can supply a significant fraction of the lipids required in autophagosome biogenesis. Our kinetic model is generally applicable to lipid-transfer experiments, in particular to proteins forming organelle contact sites in cells.

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von Bülow, S., Hummer, G.. 2020-05-14. Kinetics of Atg2-mediated lipid transfer from the ER can account for phagophore expansion. https://doi.org/10.1101/2020.05.12.090977

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