Dynamics and function of PtdIns(3)P in autophagy
- PMID: 18769109
- DOI: 10.4161/auto.6790
Dynamics and function of PtdIns(3)P in autophagy
Abstract
Phosphorylation of phosphatidylinositol (PtdIns) by PtdIns 3-kinase is essential for autophagy. However, the distribution and function of the enzymatic product, PtdIns 3-phosphate (PtdIns(3)P), has been unknown. We monitored PtdIns(3)P distribution during autophagy by live imaging, biochemistry, and electron microscopy, and found that PtdIns(3)P is massively delivered into the vacuole via autophagy. PtdIns(3)P is highly enriched as a membrane component of the elongating isolation membranes and autophagosome membranes rather than as an enclosed cargo, implying direct involvement of PtdIns(3)P in autophagosome formation. This observation also provides important basic information on the nature of the autophagosome membrane, which is still poorly understood. Notably, PtdIns(3)P is highly enriched on the inner (concave) surfaces of the isolation membrane and autophagosome compared to the outer surfaces. PtdIns(3)P is also enriched on ambiguous structures juxtaposed to the elongating tips of isolation membranes. We also investigated the function of PtdIns(3)P in autophagy, and show that PtdIns(3)P recruits the Atg18-Atg2 complex to autophagic membranes through an Atg18-PtdIns(3)P interaction. Interestingly, PtdIns(3)P is required only for the association of the Atg18-Atg2 complex to autophagic membranes but not for any subsequent functional activity of the Atg18-Atg2 complex, suggesting that PtdIns(3)P does not act allosterically on Atg18. Based on these results we discuss the function of PtdIns(3)P in autophagy.
Similar articles
-
The Atg18-Atg2 complex is recruited to autophagic membranes via phosphatidylinositol 3-phosphate and exerts an essential function.J Biol Chem. 2008 Aug 29;283(35):23972-80. doi: 10.1074/jbc.M803180200. Epub 2008 Jun 27. J Biol Chem. 2008. PMID: 18586673 Free PMC article.
-
Transport of phosphatidylinositol 3-phosphate into the vacuole via autophagic membranes in Saccharomyces cerevisiae.Genes Cells. 2008 Jun;13(6):537-47. doi: 10.1111/j.1365-2443.2008.01188.x. Genes Cells. 2008. PMID: 18533003
-
The Atg2-Atg18 complex tethers pre-autophagosomal membranes to the endoplasmic reticulum for autophagosome formation.Proc Natl Acad Sci U S A. 2018 Oct 9;115(41):10363-10368. doi: 10.1073/pnas.1806727115. Epub 2018 Sep 25. Proc Natl Acad Sci U S A. 2018. PMID: 30254161 Free PMC article.
-
Structure-based analyses reveal distinct binding sites for Atg2 and phosphoinositides in Atg18.J Biol Chem. 2012 Sep 14;287(38):31681-90. doi: 10.1074/jbc.M112.397570. Epub 2012 Jul 31. J Biol Chem. 2012. PMID: 22851171 Free PMC article.
-
Atg2: A novel phospholipid transfer protein that mediates de novo autophagosome biogenesis.Protein Sci. 2019 Jun;28(6):1005-1012. doi: 10.1002/pro.3623. Epub 2019 Apr 29. Protein Sci. 2019. PMID: 30993752 Free PMC article. Review.
Cited by
-
Coordination of membrane events during autophagy by multiple class III PI3-kinase complexes.J Cell Biol. 2009 Sep 21;186(6):773-82. doi: 10.1083/jcb.200907014. J Cell Biol. 2009. PMID: 19797076 Free PMC article. Review.
-
The Autophagy-Lysosomal Pathways and Their Emerging Roles in Modulating Proteostasis in Tumors.Cells. 2018 Dec 20;8(1):4. doi: 10.3390/cells8010004. Cells. 2018. PMID: 30577555 Free PMC article. Review.
-
The interplay of autophagy and oxidative stress in the pathogenesis and therapy of retinal degenerative diseases.Cell Biosci. 2022 Jan 3;12(1):1. doi: 10.1186/s13578-021-00736-9. Cell Biosci. 2022. PMID: 34980273 Free PMC article. Review.
-
Diversity in the regulation of autophagy and mitophagy: lessons from Parkinson's disease.Parkinsons Dis. 2011;2011:789431. doi: 10.4061/2011/789431. Epub 2011 Mar 17. Parkinsons Dis. 2011. PMID: 21603187 Free PMC article.
-
Lipid droplet and early autophagosomal membrane targeting of Atg2A and Atg14L in human tumor cells.J Lipid Res. 2014 Jul;55(7):1267-78. doi: 10.1194/jlr.M046359. Epub 2014 Apr 28. J Lipid Res. 2014. PMID: 24776541 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
