Mitochondrial p53 mediates a transcription-independent regulation of cell respiration and interacts with the mitochondrial F₁F₀-ATP synthase

Abstract : We and others previously reported that endogenous p53 can be located at mitochondria in the absence of stress, suggesting that p53 has a role in the normal physiology of this organelle. The aim of this study was to characterize in unstressed cells the intramitochondrial localization of p53 and identify new partners and functions of p53 in mitochondria. We find that the intramitochondrial pool of p53 is located in the intermembrane space and the matrix. Of note, unstressed HCT116 p53+/+ cells simultaneously show increased O₂ consumption and decreased mitochondrial superoxide production compared with their p53-null counterpart. This data was confirmed by stable H1299 cell lines expressing low levels of p53 specifically targeted to the matrix. Using immunoprecipitation and mass spectrometry, we identified the oligomycin sensitivity-conferring protein (OSCP), a subunit of the F₁F₀-ATP synthase complex, as a new partner of endogenous p53, specifically interacting with p53 localized in the matrix. Interestingly, this interaction seems implicated in mitochondrial p53 localization. Moreover, p53 localized in the matrix promotes the assembly of F₁F₀-ATP synthase. Taking into account that deregulations of mitochondrial respiration and reactive oxygen species production are tightly linked to cancer development, we suggest that mitochondrial p53 may be an important regulator of normal mitochondrial and cellular physiology, potentially exerting tumor suppression activity inside mitochondria.
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Cell Cycle, Taylor & Francis, 2014, 12 (17), pp.2781 - 2793. 〈10.4161/cc.25870〉
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https://hal.archives-ouvertes.fr/hal-01871462
Contributeur : Zhiwei Zhu <>
Soumis le : lundi 10 septembre 2018 - 19:41:50
Dernière modification le : mercredi 12 septembre 2018 - 10:14:05

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Marie Bergeaud, Lise Mathieu, Arnaud Guillaume, Ute Moll, Bernard Mignotte, et al.. Mitochondrial p53 mediates a transcription-independent regulation of cell respiration and interacts with the mitochondrial F₁F₀-ATP synthase. Cell Cycle, Taylor & Francis, 2014, 12 (17), pp.2781 - 2793. 〈10.4161/cc.25870〉. 〈hal-01871462〉

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