title: Glutamate dehydrogenase contributes to leucine sensing in the regulation of autophagy.
abstract: Amino acids, leucine in particular, are known to inhibit autophagy, at least in part by their ability to stimulate MTOR-mediated signaling. Evidence is presented showing that glutamate dehydrogenase, the central enzyme in amino acid catabolism, contributes to leucine sensing in the regulation of autophagy. The data suggest a dual mechanism by which glutamate dehydrogenase activity modulates autophagy, i.e., by activating MTORC1 and by limiting the formation of reactive oxygen species.
authors.affiliation: EA4530, Faculty of Pharmacy, University Paris-Sud, Châtenay-Malabry, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Lorin
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Tol
authors.forename: Chantal
authors.initials: C
authors.lastname: Bauvy
authors.forename: Anneke
authors.initials: A
authors.lastname: Strijland
authors.forename: Christian
authors.initials: C
authors.lastname: Poüs
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Verhoeven
authors.forename: Patrice
authors.initials: P
authors.lastname: Codogno
authors.forename: Alfred J
authors.initials: AJ
authors.lastname: Meijer
mesh_terms: D001343:Autophagy / Q000187:drug effects*; D055785:Gene Knockdown Techniques; D005969:Glutamate Dehydrogenase / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007930:Leucine / Q000494:pharmacology*; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014633:Valine / Q000494:pharmacology
chemical_list: D046912:Multiprotein Complexes; D017382:Reactive Oxygen Species; D005969:Glutamate Dehydrogenase; C561840:GLUD1 protein, human; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D007930:Leucine; D014633:Valine
keywords: AMPK; MTOR; NADPH; amino acids; mitochondria; reactive oxygen species; signaling; transhydrogenase