Mitochondrial localization of APE/Ref-1 in thyroid cells

Gianluca Tell, Enrico Crivellato, Alex Pines, Igor Paron, Carlo Pucillo, Giorgio Manzini, Antonella Bandiera, Mark R. Kelley, Carla Di Loreto, Giuseppe Damante

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

Mutations of mitochondrial DNA (mtDNA) are associated with different human diseases, including cancer and aging. Reactive oxygen species produced during oxidative phosphorylation are a major source of mtDNA damage. It is not clear, however, whether DNA repair mechanisms, able to abolish effects due to oxidative damage, are present in mitochondria. APE/Ref-1 is a nuclear protein possessing both redox activity (by which activates, "in vitro", the DNA-binding functions of several transcription factors) and DNA repair activity over apurinic/apyrimidinic sites. Immunohistochemical evidences indicate that in follicular thyroid cells, APE/Ref-1 is located in both nucleus and cytoplasm. Electronmicroscopy immunocytochemistry performed in the rat thyroid FRTL-5 cell line, indicates that part of the cytoplasmatic APE/Ref-1 is located in mitochondria. The presence of APE/Ref-1 inside mitochondria is further demonstrated by western blot analysis after cell fractionation. In the Kimol cell line (which is derived from FRTL-5, transformed by the Ki-ras oncogene) the amount of mitochondrial APE/Ref-1 is reduced by three to fourfold with respect to the normal FRTL-5 cells. These results suggest that: (i) a machinery capable of repairing DNA damaged by oxidative stress is present in mitochondria and (ii) mtDNA repair mechanisms may be impaired during cell transformation.

Original languageEnglish (US)
Pages (from-to)143-152
Number of pages10
JournalMutation Research - DNA Repair
Volume485
Issue number2
DOIs
StatePublished - Mar 7 2001

Keywords

  • APE/Ref-1
  • Base excision repair
  • Mitochondrial DNA
  • Thyroid

ASJC Scopus subject areas

  • Molecular Biology
  • Toxicology
  • Genetics

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