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      ATG2 transports lipids to promote autophagosome biogenesis

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          Valverde et al. show that the autophagy protein ATG2 functions in autophagosome biogenesis by transferring lipids at ER–autophagosome contact sites.


          During macroautophagic stress, autophagosomes can be produced continuously and in high numbers. Many different organelles have been reported as potential donor membranes for this sustained autophagosome growth, but specific machinery to support the delivery of lipid to the growing autophagosome membrane has remained unknown. Here we show that the autophagy protein, ATG2, without a clear function since its discovery over 20 yr ago, is in fact a lipid-transfer protein likely operating at the ER–autophagosome interface. ATG2A can bind tens of glycerophospholipids at once and transfers lipids robustly in vitro. An N-terminal fragment of ATG2A that supports lipid transfer in vitro is both necessary and fully sufficient to rescue blocked autophagosome biogenesis in ATG2A/ATG2B KO cells, implying that regulation of lipid homeostasis is the major autophagy-dependent activity of this protein and, by extension, that protein-mediated lipid transfer across contact sites is a principal contributor to autophagosome formation.

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          Most cited references 36

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               D Mastronarde (2005)
              A new method was developed to acquire images automatically at a series of specimen tilts, as required for tomographic reconstruction. The method uses changes in specimen position at previous tilt angles to predict the position at the current tilt angle. Actual measurement of the position or focus is skipped if the statistical error of the prediction is low enough. This method allows a tilt series to be acquired rapidly when conditions are good but falls back toward the traditional approach of taking focusing and tracking images when necessary. The method has been implemented in a program, SerialEM, that provides an efficient environment for data acquisition. This program includes control of an energy filter as well as a low-dose imaging mode, in which tracking and focusing occur away from the area of interest. The program can automatically acquire a montage of overlapping frames, allowing tomography of areas larger than the field of the CCD camera. It also includes tools for navigating between specimen positions and finding regions of interest.

                Author and article information

                J Cell Biol
                J. Cell Biol
                The Journal of Cell Biology
                Rockefeller University Press
                28 June 2019
                05 April 2019
                : 218
                : 6
                : 1787-1798
                [1 ]Department of Cell Biology, Yale University School of Medicine, New Haven, CT
                [2 ]Laboratory of Molecular Electron Microscopy, The Rockefeller University, New York, NY
                Author notes
                Correspondence to Thomas J. Melia: thomas.melia@

                D.P. Valverde and S. Yu contributed equally to this paper and the first author was selected by a coin flip.

                © 2019 Valverde et al.

                This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at

                Page count
                Pages: 12
                Funded by: National Institutes of Health, DOI,%22National%20Institutes%20of%20Health%22;
                Award ID: GM1000930
                Award ID: NS063973
                Award ID: GM080616
                Award ID: GM114068
                Funded by: China Scholarship Council, DOI;
                Funded by: National Institutes of Health, DOI;
                Award ID: T32 GM007223
                Funded by: National Science Foundation, DOI;
                Research Articles

                Cell biology


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