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α-Ketoglutarate inhibits autophagy.
| Content Provider | Europe PMC |
|---|---|
| Author | Baracco, Elisa Elena Castoldi, Francesca Durand, Sylvère Enot, David P. Tadic, Jelena Kainz, Katharina Madeo, Frank Chery, Alexis Izzo, Valentina Maiuri, Maria Chiara Pietrocola, Federico Kroemer, Guido |
| Abstract | The metabolite α-ketoglutarate is membrane-impermeable, meaning that it is usually added to cells in the form of esters such as dimethyl −ketoglutarate (DMKG), trifluoromethylbenzyl α-ketoglutarate (TFMKG) and octyl α-ketoglutarate (O-KG). Once these compounds cross the plasma membrane, they are hydrolyzed by esterases to generate α-ketoglutarate, which remains trapped within cells. Here, we systematically compared DMKG, TFMKG and O-KG for their metabolic and functional effects. All three compounds similarly increased the intracellular levels of α−ketoglutarate, yet each of them had multiple effects on other metabolites that were not shared among the three agents, as determined by mass spectrometric metabolomics. While all three compounds reduced autophagy induced by culture in nutrient-free conditions, TFMKG and O-KG (but not DMKG) caused an increase in baseline autophagy in cells cultured in complete medium. O-KG (but neither DMKG nor TFMK) inhibited oxidative phosphorylation and exhibited cellular toxicity. Altogether, these results support the idea that intracellular α-ketoglutarate inhibits starvation-induced autophagy and that it has no direct respiration-inhibitory effect. |
| Journal | Aging |
| Volume Number | 11 |
| PubMed Central reference number | PMC6594794 |
| Issue Number | 11 |
| PubMed reference number | 31173576 |
| e-ISSN | 19454589 |
| DOI | 10.18632/aging.102001 |
| Language | English |
| Publisher | Impact Journals |
| Publisher Date | 2019-06-01 |
| Access Restriction | Open |
| Rights License | This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright © 2019 Baracco et al. |
| Subject Keyword | acetyl CoA aging cell death Krebs cycle metabolomics mitochondria |
| Content Type | Text |
| Resource Type | Article |
| Subject | Aging Cell Biology |
