Dataset Information

The GID Ubiquitin Ligase Complex is a Regulator of AMPK Activity and Organismal Lifespan

ABSTRACT: The AMP-activated protein kinase (AMPK) regulates cellular energy homeostasis by sensing the metabolic status of the cell. AMPK is regulated by phosphorylation and dephosphorylation as a result of changing AMP/ATP levels and by removal of inhibitory ubiquitin residues by USP10. In this context, we identified the GID-complex, an evolutionarily conserved ubiquitin-ligasecomplex (E3), as a negative regulator of AMPK activity. Our data show that the GID-complex targets AMPK for ubiquitination thereby altering its activity. Cells depleted of GID-subunits mimic a state of starvation as shown by increased AMPK activity and autophagic flux as well as reduced MTOR activation. Consistently, gid-genes knockdown in C. elegans results in increased organismal lifespan. This study may contribute to understand metabolic disorders such as type 2 diabetes mellitus and morbid obesity and implements alternative therapeutic approaches to alter AMPK activity.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture

SUBMITTER: Alessandro Ori

LAB HEAD: Alessandro Ori

PROVIDER: PXD015170 | Pride | 2021-09-08

REPOSITORIES: Pride

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			Action	DRS
	181026_IH_AO_S01_WT0hRep1_dc.raw	Raw
	181026_IH_AO_S02_WT2hRep1_dc.raw	Raw
	181026_IH_AO_S03_WT6hRep1_dc.raw	Raw
	181026_IH_AO_S04_WT0hRep2_dc.raw	Raw
	181026_IH_AO_S05_WT2hRep2_dc.raw	Raw

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Publications

The GID ubiquitin ligase complex is a regulator of AMPK activity and organismal lifespan.

Liu Huaize H Ding Jie J Köhnlein Karl K Urban Nadine N Ori Alessandro A Villavicencio-Lorini Pablo P Walentek Peter P Klotz Lars-Oliver LO Hollemann Thomas T Pfirrmann Thorsten T

Autophagy 20191203 9

The AMP-activated protein kinase (AMPK) regulates cellular energy homeostasis by sensing the metabolic status of the cell. AMPK is regulated by phosphorylation and dephosphorylation as a result of changing AMP/ATP levels and by removal of inhibitory ubiquitin residues by USP10. In this context, we identified the GID-complex, an evolutionarily conserved ubiquitin-ligase-complex (E3), as a negative regulator of AMPK activity. Our data show that the GID-complex targets AMPK for ubiquitination there ...[more]

PMID: 31795790

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