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.
Author: | Sören von BülowORCiDGND, Gerhard HummerORCiD |
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URN: | urn:nbn:de:hebis:30:3-727528 |
DOI: | https://doi.org/10.1101/2020.05.12.090977 |
Parent Title (English): | bioRxiv |
Document Type: | Preprint |
Language: | English |
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 |
Issue: | 2020.05.12.090977 |
Page Number: | 14 |
HeBIS-PPN: | 509917240 |
Institutes: | Physik |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
Sammlungen: | Universitätspublikationen |
Licence (German): | Creative Commons - CC BY-ND - Namensnennung - Keine Bearbeitungen 4.0 International |