| Added by | llecam |
|---|---|
| Last modified by | ircm doc |
| Group name | EquipeLLC |
| Item Type | Journal Article |
| Title | Mitochondrial MDM2 Regulates Respiratory Complex I Activity Independently of p53 |
| Creator | Arena et al. |
| Author | Giuseppe Arena |
| Author | Madi Yann Cissé |
| Author | Samuel Pyrdziak |
| Author | Laurent Chatre |
| Author | Romain Riscal |
| Author | Maryse Fuentes |
| Author | Jamie Jon Arnold |
| Author | Markus Kastner |
| Author | Laurie Gayte |
| Author | Christelle Bertrand-Gaday |
| Author | Kevin Nay |
| Author | Claire Angebault-Prouteau |
| Author | Kerren Murray |
| Author | Beatrice Chabi |
| Author | Christelle Koechlin-Ramonatxo |
| Author | Béatrice Orsetti |
| Author | Charles Vincent |
| Author | Jean-Christophe Marine |
| Author | Sandrine Etienne-Manneville |
| Author | Florence Bernex |
| Author | Anne Lombès |
| Author | Craig Eugene Cameron |
| Author | Hervé Dubouchaud |
| Author | Miria Ricchetti |
| Author | Laetitia Karine Linares |
| Author | Laurent Le Cam |
| Abstract | Accumulating evidence indicates that the MDM2 oncoprotein promotes tumorigenesis beyond its canonical negative effects on the p53 tumor suppressor, but these p53-independent functions remain poorly understood. Here, we show that a fraction of endogenous MDM2 is actively imported in mitochondria to control respiration and mitochondrial dynamics independently of p53. Mitochondrial MDM2 represses the transcription of NADH-dehydrogenase 6 (MT-ND6) in vitro and in vivo, impinging on respiratory complex I activity and enhancing mitochondrial ROS production. Recruitment of MDM2 to mitochondria increases during oxidative stress and hypoxia. Accordingly, mice lacking MDM2 in skeletal muscles exhibit higher MT-ND6 levels, enhanced complex I activity, and increased muscular endurance in mild hypoxic conditions. Furthermore, increased mitochondrial MDM2 levels enhance the migratory and invasive properties of cancer cells. Collectively, these data uncover a previously unsuspected function of the MDM2 oncoprotein in mitochondria that play critical roles in skeletal muscle physiology and may contribute to tumor progression. |
| Publication | Molecular Cell |
| Volume | 69 |
| Issue | 4 |
| Pages | 594-609.e8 |
| Date | Feb 15, 2018 |
| Journal Abbr | Mol. Cell |
| Language | eng |
| DOI | 10.1016/j.molcel.2018.01.023 |
| ISSN | 1097-4164 |
| Library Catalog | PubMed |
| Extra | PMID: 29452639 |
| Tags | first-last-corresponding, original, top |
| Date Added | 2018/12/07 - 15:31:17 |
| Date Modified | 2025/01/09 - 15:21:56 |
| Notes and Attachments | PubMed entry (Attachment) |
Institut de Recherche en Cancérologie de
