α-Ketoglutarate inhibits autophagy

• DOI: 10.18632/aging.102001
• Publication Date: 2019-06-07T15:38:00Z
• Authors: Elisa Elena Baracco; Francesca Castoldi; Sylvère Durand; David P. Enot; Jelena Tadic; Katharina Kainz; Frank Madeo; Alexis Chery; Valentina Izzo; Maria Chiara Maiuri; Federico Pietrocola; Guido Kroemer
• Keywords: Alpha ketoglutarate; Metabolic pathway

The metabolite α-ketoglutarate is membrane-impermeable, meaning that it usually added to cells in the form of esters such as dimethyl (DMKG), trifluoromethylbenzyl (TFMKG) and octyl (O-KG).Once these compounds cross plasma membrane, they are hydrolyzed by esterases generate α-ketoglutarate, which remains trapped within cells.Here, we systematically compared DMKG, TFMKG O-KG for their metabolic functional effects.All three similarly increased intracellular levels yet each them had multiple effects on other metabolites were not shared among agents, determined mass spectrometric metabolomics.While all reduced autophagy induced culture nutrient-free conditions, (but DMKG) caused an increase baseline cultured complete medium.O-KG neither DMKG nor TFMK) inhibited oxidative phosphorylation exhibited cellular toxicity.Altogether, results support idea inhibits starvation-induced has no direct respiration-inhibitory effect.