title: Dual regulation of energy metabolism by p53 in human cervix and breast cancer cells.
abstract: The role of p53 as modulator of OxPhos and glycolysis was analyzed in HeLa-L (cells containing negligible p53 protein levels) and HeLa-H (p53-overexpressing) human cervix cancer cells under normoxia and hypoxia. In normoxia, functional p53, mitochondrial enzyme contents, mitochondrial electrical potential (ΔΨm) and OxPhos flux increased in HeLa-H vs. HeLa-L cells; whereas their glycolytic enzyme contents and glycolysis flux were unchanged. OxPhos provided more than 70% of the cellular ATP and proliferation was abolished by anti-mitochondrial drugs in HeLa-H cells. In hypoxia, both cell proliferations were suppressed, but HeLa-H cells exhibited a significant decrease in OxPhos protein contents, ΔΨm and OxPhos flux. Although glycolytic function was also diminished vs. HeLa-L cells in hypoxia, glycolysis provided more than 60% of cellular ATP in HeLa-H cells. The energy metabolism phenotype of HeLa-H cells was reverted to that of HeLa-L cells by incubating with pifithrin-α, a p53-inhibitor. In normoxia, the energy metabolism phenotype of breast cancer MCF-7 cells was similar to that of HeLa-H cells, whereas p53shRNAMCF-7 cells resembled the HeLa-L cell phenotype. In hypoxia, autophagy proteins and lysosomes contents increased 2-5 times in HeLa-H cells suggesting mitophagy activation. These results indicated that under normoxia p53 up-regulated OxPhos without affecting glycolysis, whereas under hypoxia, p53 down-regulated both OxPhos (severely) and glycolysis (weakly). These p53 effects appeared mediated by the formation of p53-HIF-1α complexes. Therefore, p53 exerts a dual and contrasting regulatory role on cancer energy metabolism, depending on the O₂level.
authors.affiliation: Departamento de Bioquímica, Instituto Nacional de Cardiología, Mexico.
authors.forename: Ileana
authors.initials: I
authors.lastname: Hernández-Reséndiz
authors.affiliation: Laboratorio de Biología y Genética Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional- Zacatenco, Mexico.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Román-Rosales
authors.affiliation: Laboratorio de Biología y Genética Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional- Zacatenco, Mexico.
authors.forename: Enríque
authors.initials: E
authors.lastname: García-Villa
authors.affiliation: Laboratorio de Líquido Sinovial, Instituto Nacional de Rehabilitación, Mexico.
authors.forename: Ambar
authors.initials: A
authors.lastname: López-Macay
authors.affiliation: Departamento de Bioquímica, Instituto Nacional de Cardiología, Mexico.
authors.forename: Erika
authors.initials: E
authors.lastname: Pineda
authors.affiliation: Departamento de Bioquímica, Instituto Nacional de Cardiología, Mexico.
authors.forename: Emma
authors.initials: E
authors.lastname: Saavedra
authors.affiliation: Departamento de Bioquímica, Instituto Nacional de Cardiología, Mexico.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Gallardo-Pérez
authors.affiliation: Laboratorio de Biología y Genética Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional- Zacatenco, Mexico.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Alvarez-Ríos
authors.affiliation: Laboratorio de Biología y Genética Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional- Zacatenco, Mexico.
authors.forename: Patricio
authors.initials: P
authors.lastname: Gariglio
authors.affiliation: Departamento de Bioquímica, Instituto Nacional de Cardiología, Mexico.
authors.forename: Rafael
authors.initials: R
authors.lastname: Moreno-Sánchez
authors.affiliation: Departamento de Bioquímica, Instituto Nacional de Cardiología, Mexico. Electronic address: saren960201@hotmail.com.
authors.forename: Sara
authors.initials: S
authors.lastname: Rodríguez-Enríquez
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division; D015687:Cell Hypoxia; D004734:Energy Metabolism; D005260:Female; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: Glycolysis; Hypoxia; Oxidative phosphorylation; Tumor cells; p53