Mitochondrial localization of APE/Ref-1 in thyroid cells

G. Tell, E. Crivellato, A. Pines, I. Paron, C. Pucillo, G. Manzini, A. Bandiera, Mark Kelley, C. Di Loreto, G. Damante

Research output: Contribution to journalArticle

63 Citations (Scopus)

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

Fingerprint

Mitochondria
Thyroid Gland
Mitochondrial DNA
DNA Repair
Repair
DNA
Cells
Far-Western Blotting
Cell Fractionation
Cell Line
Oxidative stress
ras Genes
Oxidative Phosphorylation
Fractionation
Nuclear Proteins
DNA Damage
Oxidation-Reduction
Machinery
Rats
Reactive Oxygen Species

Keywords

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

ASJC Scopus subject areas

  • Toxicology
  • Genetics
  • Molecular Biology

Cite this

Tell, G., Crivellato, E., Pines, A., Paron, I., Pucillo, C., Manzini, G., ... Damante, G. (2001). Mitochondrial localization of APE/Ref-1 in thyroid cells. Mutation Research - DNA Repair, 485(2), 143-152. https://doi.org/10.1016/S0921-8777(00)00068-9

Mitochondrial localization of APE/Ref-1 in thyroid cells. / Tell, G.; Crivellato, E.; Pines, A.; Paron, I.; Pucillo, C.; Manzini, G.; Bandiera, A.; Kelley, Mark; Di Loreto, C.; Damante, G.

In: Mutation Research - DNA Repair, Vol. 485, No. 2, 07.03.2001, p. 143-152.

Research output: Contribution to journalArticle

Tell, G, Crivellato, E, Pines, A, Paron, I, Pucillo, C, Manzini, G, Bandiera, A, Kelley, M, Di Loreto, C & Damante, G 2001, 'Mitochondrial localization of APE/Ref-1 in thyroid cells', Mutation Research - DNA Repair, vol. 485, no. 2, pp. 143-152. https://doi.org/10.1016/S0921-8777(00)00068-9
Tell G, Crivellato E, Pines A, Paron I, Pucillo C, Manzini G et al. Mitochondrial localization of APE/Ref-1 in thyroid cells. Mutation Research - DNA Repair. 2001 Mar 7;485(2):143-152. https://doi.org/10.1016/S0921-8777(00)00068-9
Tell, G. ; Crivellato, E. ; Pines, A. ; Paron, I. ; Pucillo, C. ; Manzini, G. ; Bandiera, A. ; Kelley, Mark ; Di Loreto, C. ; Damante, G. / Mitochondrial localization of APE/Ref-1 in thyroid cells. In: Mutation Research - DNA Repair. 2001 ; Vol. 485, No. 2. pp. 143-152.
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