Decoding the function of Atg13 phosphorylation reveals a role of Atg11 in bulk autophagy initiation
Abstract: Autophagy is initiated by the assembly of multiple autophagy-related proteins that form the phagophore assembly site where autophagosomes are formed. Atg13 is essential early in this process, and a hub of extensive phosphorylation. How these multiple phosphorylations contribute to autophagy initiation, however, is not well understood. Here we comprehensively analyze the role of phosphorylation events on Atg13 during nutrient-rich conditions and nitrogen starvation. We identify and functionally characterize 48 in vivo phosphorylation sites on Atg13. By generating reciprocal mutants, which mimic the dephosphorylated active and phosphorylated inactive state of Atg13, we observe that disrupting the dynamic regulation of Atg13 leads to insufficient or excessive autophagy, which are both detrimental to cell survival. We furthermore demonstrate an involvement of Atg11 in bulk autophagy even during nitrogen starvation, where it contributes together with Atg1 to the multivalency that drives phase separation of the phagophore assembly site. These findings reveal the importance of post-translational regulation on Atg13 early during autophagy initiation, which provides additional layers of regulation to control bulk autophagy activity and integrate cellular signals
- Location
-
Deutsche Nationalbibliothek Frankfurt am Main
- Extent
-
Online-Ressource
- Language
-
Englisch
- Notes
-
EMBO reports. - 25, 2 (2024) , 813-831, ISSN: 1469-3178
- Classification
-
Medizin, Gesundheit
- Event
-
Veröffentlichung
- (where)
-
Freiburg
- (who)
-
Universität
- (when)
-
2024
- Creator
-
Bhattacharya, Anuradha
Torggler, Raffaela
Reiter, Wolfgang
Romanov, Natalie
Licheva, Mariya
Ciftci, Akif
Mari, Muriel
Kolb, Lena
Kaiser, Dominik
Reggiori, Fulvio
Ammerer, Gustav
Hollenstein, David M.
Kraft, Claudine
- DOI
-
10.1038/s44319-023-00055-9
- URN
-
urn:nbn:de:bsz:25-freidok-2435168
- Rights
-
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
-
25.03.2025, 1:46 PM CET
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Bhattacharya, Anuradha
- Torggler, Raffaela
- Reiter, Wolfgang
- Romanov, Natalie
- Licheva, Mariya
- Ciftci, Akif
- Mari, Muriel
- Kolb, Lena
- Kaiser, Dominik
- Reggiori, Fulvio
- Ammerer, Gustav
- Hollenstein, David M.
- Kraft, Claudine
- Universität
Time of origin
- 2024
Other Objects (12)
Biochemical reconstitution of human autophagy initiation
HORMA domain proteins in Autophagy initiation
Beclin 1 phosphorylation – at the center of autophagy regulation
ULK1-mediated phosphorylation regulates the conserved role of YKT6 in autophagy
Phosphorylation-dependent regulation of ubiquitin-binding protein optineurin in selective autophagy
Phosphorylation of Beclin 1 by BCR-ABL suppresses autophagy in CML
Spatial control of avidity regulates initiation and progression of selective autophagy
Phosphorylation of the mitochondrial autophagy receptor Nix enhances its interaction with LC3 proteins
Phosphorylation of BECLIN-1 by BCR-ABL suppresses autophagy in chronic myeloid leukemia
Early steps in autophagy depend on direct phosphorylation of Atg9 by the Atg1 kinase
In vitro reconstitution of the Atg1-kinase complex: Revealing the molecular mechanism of autophagy initiation
Decoding.Moser.
Biochemical reconstitution of human autophagy initiation
HORMA domain proteins in Autophagy initiation
Beclin 1 phosphorylation – at the center of autophagy regulation
ULK1-mediated phosphorylation regulates the conserved role of YKT6 in autophagy
Phosphorylation-dependent regulation of ubiquitin-binding protein optineurin in selective autophagy
Phosphorylation of Beclin 1 by BCR-ABL suppresses autophagy in CML
Spatial control of avidity regulates initiation and progression of selective autophagy
Phosphorylation of the mitochondrial autophagy receptor Nix enhances its interaction with LC3 proteins
Phosphorylation of BECLIN-1 by BCR-ABL suppresses autophagy in chronic myeloid leukemia
Early steps in autophagy depend on direct phosphorylation of Atg9 by the Atg1 kinase
In vitro reconstitution of the Atg1-kinase complex: Revealing the molecular mechanism of autophagy initiation
Decoding.Moser.
Biochemical reconstitution of human autophagy initiation
HORMA domain proteins in Autophagy initiation
Beclin 1 phosphorylation – at the center of autophagy regulation
ULK1-mediated phosphorylation regulates the conserved role of YKT6 in autophagy
Phosphorylation-dependent regulation of ubiquitin-binding protein optineurin in selective autophagy
Phosphorylation of Beclin 1 by BCR-ABL suppresses autophagy in CML
Spatial control of avidity regulates initiation and progression of selective autophagy
Phosphorylation of the mitochondrial autophagy receptor Nix enhances its interaction with LC3 proteins
Phosphorylation of BECLIN-1 by BCR-ABL suppresses autophagy in chronic myeloid leukemia
Early steps in autophagy depend on direct phosphorylation of Atg9 by the Atg1 kinase
In vitro reconstitution of the Atg1-kinase complex: Revealing the molecular mechanism of autophagy initiation