Glucose starvation induces autophagy via ULK1-mediated activation of PIKfyve in an AMPK-dependent manner
| Autor: | Cansu Karabiyik, Sung Min Son, David C. Rubinsztein, Mariella Vicinanza |
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| Přispěvatelé: | Karabiyik, Cansu [0000-0001-7993-1825], Son, Sungmin [0000-0002-3536-1952], Rubinsztein, David [0000-0001-5002-5263], Apollo - University of Cambridge Repository |
| Rok vydání: | 2021 |
| Předmět: |
AMPK
autophagy glucose starvation Biology General Biochemistry Genetics and Molecular Biology Cell Line 03 medical and health sciences PIKFYVE Phosphatidylinositol 3-Kinases 0302 clinical medicine Downregulation and upregulation AMP-Activated Protein Kinase Kinases Phosphatidylinositol Phosphates Autophagy-Related Protein-1 Homolog Humans Protein kinase A Molecular Biology PI3K/AKT/mTOR pathway Phospholipids 030304 developmental biology ULK1 0303 health sciences phagophore Kinase PI(5)P Autophagy Autophagosomes Cell Biology PIKfyve Cell biology Glucose Metabolism Gene Expression Regulation mTOR Protein Kinases 030217 neurology & neurosurgery Developmental Biology Signal Transduction |
| Popis: | Autophagy is an essential catabolic process induced to provide cellular energy sources in response to nutrient limitation through the activation of kinases, like AMP-activated protein kinase (AMPK) and ULK1. Although glucose starvation induces autophagy, the exact mechanism underlying this signaling has yet to be elucidated. Here, we reveal a role for ULK1 in non-canonical autophagy signaling using diverse cell lines. ULK1 activated by AMPK during glucose starvation phosphorylates the lipid kinase PIKfyve on S1548, thereby increasing its activity and the synthesis of the phospholipid PI(5)P without changing the levels of PI(3,5)P2. ULK1-mediated activation of PIKfyve enhances the formation of PI(5)P-containing autophagosomes upon glucose starvation, resulting in an increase in autophagy flux. Phospho-mimic PIKfyve S1548D drives autophagy upregulation and lowers autophagy substrate levels. Our study has identified how ULK1 upregulates autophagy upon glucose starvation and induces the formation of PI(5)P-containing autophagosomes by activating PIKfyve. |
| Databáze: | OpenAIRE |
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