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-ligase-complex (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 macroautophagic/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

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: Autophagy. - 16, 9 (2020) , 1618-1634, ISSN: 1554-8635

Classification and Topics

• Keyword: Autophagie ; Langlebigkeit ; Ubiquitinierung

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2020
• Creator: Liu, Huaize ; Ding, Jie ; Köhnlein, Karl ; Urban, Nadine ; Ori, Alessandro ; Villavicencio Lorini, Pablo ; Walentek, Peter ; Klotz, Lars-Oliver ; Hollemann, Thomas ; Pfirrmann, Thorsten

Further information

• DOI: 10.1080/15548627.2019.1695399
• URN: urn:nbn:de:bsz:25-freidok-1674221
• Rights: Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 25.03.2025, 1:44 PM CET