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Arena 2018 Mol Cell
Additional label Labels  + , 2018-03  +
Coupling states OXPHOS  +
Diseases Cancer  +
Has abstract Accumulating evidence indicates that the M
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.
y and may contribute to tumor progression.  +
Has editor [[Kandolf G]]  +
Has info [ PMID: 29452639 Open Access]; »[[File:O2k-brief.png|36px|link= |O2k-brief]]  +
Has publicationkeywords MDM2  + , MT-ND6  + , Hypoxia  + , Migration  + , Mitochondria  + , Respiratory complex I  +
Has title Arena G, Cissé MY, Pyrdziak S, Chatre L, R
Arena G, Cissé MY, Pyrdziak S, Chatre L, Riscal R, Fuentes M, Arnold JJ, Kastner M, Gayte L, Bertrand-Gaday C, Nay K, Angebault-Prouteau C, Murray K, Chabi B, Koechlin-Ramonatxo C, Orsetti B, Vincent C, Casas F, Marine JC, Etienne-Manneville S, Bernex F, Lombès A, Cameron CE, Dubouchaud H, Ricchetti M, Linares LK, Le Cam L (2018) Mitochondrial MDM2 regulates respiratory complex I activity independently of p53. Mol Cell 69:594-609.
independently of p53. Mol Cell 69:594-609.  +
Instrument and method Oxygraph-2k  +
Mammal and model Human  +
MiP area Respiration  +
Pathways N  + , S  + , NS  +
Preparation Permeabilized cells  +
Tissue and cell Lung;gill  + , Other cell lines  +
Was published by MiPNetLab FR Montpellier Wrutniak-Cabello C +
Was published in journal Mol Cell +
Was published in year 2018  +
Was written by Arena G + , Cisse MY + , Pyrdziak S + , Chatre L + , Riscal R + , Fuentes M + , Arnold JJ + , Kastner M + , Gayte L + , Bertrand-Gaday C + , Nay K + , Angebault-Prouteau C + , Murray K + , Chabi B + , Koechlin-Ramonatxo C + , Orsetti B + , Vincent C + , Casas F + , Marine JC + , Etienne-Manneville S + , Bernex F + , Lombes A + , Cameron CE + , Dubouchaud H + , Ricchetti M + , Linares LK + , Le Cam L +
Categories Publications
Modification date
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09:54:44, 10 April 2019  +
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