Repository logo
 

Glucose starvation induces autophagy via ULK1-mediated activation of PIKfyve in an AMPK-dependent manner.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Vicinanza, Mariella 
Son, Sung Min 
Rubinsztein, David C 

Abstract

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.

Description

Keywords

AMPK, PI(5)P, PIKfyve, ULK1, autophagy, glucose starvation, mTOR, phagophore, AMP-Activated Protein Kinase Kinases, Autophagosomes, Autophagy, Autophagy-Related Protein-1 Homolog, Cell Line, Gene Expression Regulation, Glucose, Humans, Metabolism, Phosphatidylinositol 3-Kinases, Phosphatidylinositol Phosphates, Phospholipids, Protein Kinases, Signal Transduction

Journal Title

Dev Cell

Conference Name

Journal ISSN

1534-5807
1878-1551

Volume Title

56

Publisher

Elsevier BV
Sponsorship
UK Dementia Research Institute (funded by the MRC, Alzheimer’s Research UK and the Alzheimer’s Society) (to DCR), Roger de Spoelberch Foundation (DCR) and the Gates Cambridge Scholarship (CK)