Transmembrane phospholipid translocation mediated by Atg9 is involved in autophagosome formation
Open Access
- 13 January 2021
- journal article
- research article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 220 (3)
- https://doi.org/10.1083/jcb.202009194
Abstract
The mechanism of isolation membrane formation in autophagy is receiving intensive study. We recently found that Atg9 translocates phospholipids across liposomal membranes and proposed that this functionality plays an essential role in the expansion of isolation membranes. The distribution of phosphatidylinositol 3-phosphate in both leaflets of yeast autophagosomal membranes supports this proposal, but if Atg9-mediated lipid transport is crucial, symmetrical distribution in autophagosomes should be found broadly for other phospholipids. To test this idea, we analyzed the distributions of phosphatidylcholine, phosphatidylserine, and phosphatidylinositol 4-phosphate by freeze-fracture electron microscopy. We found that all these phospholipids are distributed with comparable densities in the two leaflets of autophagosomes and autophagic bodies. Moreover, de novo–synthesized phosphatidylcholine is incorporated into autophagosomes preferentially and shows symmetrical distribution in autophagosomes within 30 min after synthesis, whereas this symmetrical distribution is compromised in yeast expressing an Atg9 mutant. These results indicate that transbilayer phospholipid movement that is mediated by Atg9 is involved in the biogenesis of autophagosomes.Keywords
Funding Information
- Japan Society of the Promotion of Science (18K15004, 19K07265, 20H05339, 15H05902, 18H04023)
This publication has 48 references indexed in Scilit:
- ER exit sites are physical and functional core autophagosome biogenesis componentsMolecular Biology of the Cell, 2013
- The Role of Lipids in the Control of AutophagyCurrent Biology, 2013
- Atg9 vesicles are an important membrane source during early steps of autophagosome formationThe Journal of cell biology, 2012
- Dynamic and transient interactions of Atg9 with autophagosomes, but not membrane integration, are required for autophagyMolecular Biology of the Cell, 2012
- Mammalian Atg2 proteins are essential for autophagosome formation and important for regulation of size and distribution of lipid dropletsMolecular Biology of the Cell, 2012
- Metabolism and Regulation of Glycerolipids in the Yeast Saccharomyces cerevisiaeGenetics, 2012
- Intracellular phosphatidylserine is essential for retrograde membrane traffic through endosomesProceedings of the National Academy of Sciences of the United States of America, 2011
- Metabolic labeling and direct imaging of choline phospholipids in vivoProceedings of the National Academy of Sciences of the United States of America, 2009
- Rab1 Guanine Nucleotide Exchange Factor SidM Is a Major Phosphatidylinositol 4-Phosphate-binding Effector Protein of Legionella pneumophilaJournal of Biological Chemistry, 2009
- Synthesis and function of membrane phosphoinositides in budding yeast, Saccharomyces cerevisiaeBiochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 2007