| Added by | mollevi |
|---|---|
| Last modified by | standudu |
| Group name | EquipeLLC |
| Item Type | Journal Article |
| Title | E4F1 controls a transcriptional program essential for pyruvate dehydrogenase activity |
| Creator | Lacroix et al. |
| Author | M. Lacroix |
| Author | G. Rodier |
| Author | O. Kirsh |
| Author | T. Houles |
| Author | H. Delpech |
| Author | B. Seyran |
| Author | L. Gayte |
| Author | F. Casas |
| Author | L. Pessemesse |
| Author | M. Heuillet |
| Author | F. Bellvert |
| Author | J. C. Portais |
| Author | C. Berthet |
| Author | F. Bernex |
| Author | M. Brivet |
| Author | A. Boutron |
| Author | L. Le Cam |
| Author | C. Sardet |
| Abstract | The mitochondrial pyruvate dehydrogenase (PDH) complex (PDC) acts as a central metabolic node that mediates pyruvate oxidation and fuels the tricarboxylic acid cycle to meet energy demand. Here, we reveal another level of regulation of the pyruvate oxidation pathway in mammals implicating the E4 transcription factor 1 (E4F1). E4F1 controls a set of four genes [dihydrolipoamide acetlytransferase (Dlat), dihydrolipoyl dehydrogenase (Dld), mitochondrial pyruvate carrier 1 (Mpc1), and solute carrier family 25 member 19 (Slc25a19)] involved in pyruvate oxidation and reported to be individually mutated in human metabolic syndromes. E4F1 dysfunction results in 80% decrease of PDH activity and alterations of pyruvate metabolism. Genetic inactivation of murine E4f1 in striated muscles results in viable animals that show low muscle PDH activity, severe endurance defects, and chronic lactic acidemia, recapitulating some clinical symptoms described in PDC-deficient patients. These phenotypes were attenuated by pharmacological stimulation of PDH or by a ketogenic diet, two treatments used for PDH deficiencies. Taken together, these data identify E4F1 as a master regulator of the PDC. |
| Publication | Proc Natl Acad Sci U S A |
| Volume | 113 |
| Pages | 10998-1003 |
| Date | Sep 27 2016 |
| Journal Abbr | Proceedings of the National Academy of Sciences of the United States of America |
| DOI | 10.1073/pnas.1602754113 |
| ISSN | 1091-6490 (Electronic) 0027-8424 (Linking) |
| Tags | first, first-last-corresponding, original |
| Date Added | 2018/11/14 - 11:59:48 |
| Date Modified | 2022/08/30 - 16:28:14 |
| Notes and Attachments | (Note) (Note) 27621446 (Attachment) |
Institut de Recherche en Cancérologie de
