| Added by | lklinares |
|---|---|
| Group name | EquipeLL |
| Item Type | Journal Article |
| Title | E4F1-mediated control of pyruvate dehydrogenase activity is essential for skin homeostasis |
| Creator | Goguet-Rubio et al. |
| Author | Perrine Goguet-Rubio |
| Author | Berfin Seyran |
| Author | Laurie Gayte |
| Author | Florence Bernex |
| Author | Anne Sutter |
| Author | Hélène Delpech |
| Author | Laetitia Karine Linares |
| Author | Romain Riscal |
| Author | Cendrine Repond |
| Author | Geneviève Rodier |
| Author | Olivier Kirsh |
| Author | Jawida Touhami |
| Author | Jean Noel |
| Author | Charles Vincent |
| Author | Nelly Pirot |
| Author | Guillaume Pavlovic |
| Author | Yann Herault |
| Author | Marc Sitbon |
| Author | Luc Pellerin |
| Author | Claude Sardet |
| Author | Matthieu Lacroix |
| Author | Laurent Le Cam |
| Abstract | The multifunctional protein E4 transcription factor 1 (E4F1) is an essential regulator of epidermal stem cell (ESC) maintenance. Here, we found that E4F1 transcriptionally regulates a metabolic program involved in pyruvate metabolism that is required to maintain skin homeostasis. E4F1 deficiency in basal keratinocytes resulted in deregulated expression of dihydrolipoamide acetyltransferase (Dlat), a gene encoding the E2 subunit of the mitochondrial pyruvate dehydrogenase (PDH) complex. Accordingly, E4f1 knock-out (KO) keratinocytes exhibited impaired PDH activity and a redirection of the glycolytic flux toward lactate production. The metabolic reprogramming of E4f1 KO keratinocytes associated with remodeling of their microenvironment and alterations of the basement membrane, led to ESC mislocalization and exhaustion of the ESC pool. ShRNA-mediated depletion of Dlat in primary keratinocytes recapitulated defects observed upon E4f1 inactivation, including increased lactate secretion, enhanced activity of extracellular matrix remodeling enzymes, and impaired clonogenic potential. Altogether, our data reveal a central role for Dlat in the metabolic program regulated by E4F1 in basal keratinocytes and illustrate the importance of PDH activity in skin homeostasis. |
| Publication | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 113 |
| Issue | 39 |
| Pages | 11004-11009 |
| Date | 09 27, 2016 |
| Journal Abbr | Proc Natl Acad Sci U S A |
| Language | eng |
| DOI | 10.1073/pnas.1602751113 |
| ISSN | 1091-6490 |
| Library Catalog | PubMed |
| Extra | PMID: 27621431 PMCID: PMC5047149 |
| Tags | Animals, Animals, Newborn, Basement Membrane, Cell Adhesion, Cells, Cultured, Cellular Microenvironment, Dihydrolipoyllysine-Residue Acetyltransferase, DNA-Binding Proteins, E4F1, Epidermal Cells, Epidermis, Gene Expression Regulation, Homeostasis, Keratinocytes, Mice, Knockout, Mitochondrial Proteins, Monocarboxylic Acid Transporters, Muscle Proteins, original, PDH, pyruvate, Pyruvates, Repressor Proteins, RNA, Messenger, Skin, stem cell, Stem Cells, Transcription Factors, Ubiquitin-Protein Ligases |
| Date Added | 2024/12/03 - 09:12:56 |
| Date Modified | 2024/12/03 - 09:12:56 |
| Notes and Attachments | PubMed entry (Attachment) Texte intégral (Attachment) |
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