title: Mitochondrial matrix P53 sensitizes cells to oxidative stress.
abstract: A mitochondrial matrix-specific p53 construct (termed p53-290) in HepG2 cells was utilized to determine the impact of p53 in the mitochondrial matrix following oxidative stress. H₂O₂ exposure reduced cellular proliferation similarly in both p53-290 and vector cells, and p53-290 cells demonstrating decreased cell viability at 1mM H₂O₂ (~85% viable). Mitochondrial DNA (mtDNA) abundance was decreased in a dose-dependent manner in p53-290 cells while no change was observed in vector cells. Oximetric analysis revealed reduced maximal respiration and reserve capacity in p53-290 cells. Our results demonstrate that mitochondrial matrix p53 sensitizes cells to oxidative stress by reducing mtDNA abundance and mitochondrial function.
authors.affiliation: Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Koczor
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Torres
authors.forename: Earl J
authors.initials: EJ
authors.lastname: Fields
authors.forename: Amy
authors.initials: A
authors.lastname: Boyd
authors.forename: William
authors.initials: W
authors.lastname: Lewis
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53; D006861:Hydrogen Peroxide