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

  • 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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Author:Sören von BülowORCiDGND, Gerhard HummerORCiD
Parent Title (English):bioRxiv
Document Type:Preprint
Date of Publication (online):2020/05/14
Date of first Publication:2020/05/14
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2023/03/24
Page Number:14
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Licence (German):License LogoCreative Commons - CC BY-ND - Namensnennung - Keine Bearbeitungen 4.0 International