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Deacetylation of nuclear LC3 drives autophagy initiation under starvation.
- Source :
-
Molecular cell [Mol Cell] 2015 Feb 05; Vol. 57 (3), pp. 456-66. Date of Electronic Publication: 2015 Jan 15. - Publication Year :
- 2015
-
Abstract
- Shuttling of macromolecules between different cellular compartments helps regulate the timing and extent of different cellular activities. Here, we report that LC3, a key initiator of autophagy that cycles between the nucleus and cytoplasm, becomes selectively activated in the nucleus during starvation through deacetylation by the nuclear deacetylase Sirt1. Deacetylation of LC3 at K49 and K51 by Sirt1 allows LC3 to interact with the nuclear protein DOR and return to the cytoplasm with DOR, where it is able to bind Atg7 and other autophagy factors and undergo phosphatidylethanolamine conjugation to preautophagic membranes. The association of deacetylated LC3 with autophagic factors shifts LC3's distribution from the nucleus toward the cytoplasm. Thus, an acetylation-deacetylation cycle ensures that LC3 effectively redistributes in an activated form from nucleus to cytoplasm, where it plays a central role in autophagy to enable the cell to cope with the lack of external nutrients.<br /> (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Subjects :
- Acetylation
Autophagy-Related Protein 7
Cytoplasm metabolism
HEK293 Cells
HeLa Cells
Humans
Microscopy, Confocal
Microtubule-Associated Proteins genetics
Microtubule-Associated Proteins ultrastructure
Ubiquitin-Activating Enzymes metabolism
Autophagy
Cell Nucleus metabolism
Lysine metabolism
Microtubule-Associated Proteins metabolism
Sirtuin 1 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4164
- Volume :
- 57
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Molecular cell
- Publication Type :
- Academic Journal
- Accession number :
- 25601754
- Full Text :
- https://doi.org/10.1016/j.molcel.2014.12.013