Mitochondrial DNA damage under oxidative stress conditions is closely related to inner membrane permeabilization

A. M. Almeida, N. C. Souza-Pinto, C. R. Bertoncini, I. L. Nantes, A. E. Vercesi

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The mtDNA is a 16,000 base pair closed supercoiled molecule that codes for respiratory chain enzymes, and RNAs. The lack of protective histones, short repair mechanisms and be transiently attached to the inner membrane, make the mitochondrial genetic material particularly susceptible to oxidative damage. In this work we detected and characterized mtDNA damage in mitochondria exposed to situations of oxidative stress. The oxidant systems utilize: lipid peroxidation initiators (the Fe2+-citrate complex and diphenylacetatdehyde) and a Ca2+-dependent membrane transition pore (MTP) inducer (diamide, a thiol oxidant). Agarose gel electrophoresis showed mtDNA breakage in all cases in which the inner membrane permeability was altered. When lipid peroxidation occurred, evidenced by TBARS enhancement and Schiff bases formation, DNA adducts with aldehydes - products of fatty acids oxidation - were also observed. Through postlabeling assay and 8OhdG measure, the OH participation in DNA breakage induced by Fe2+-citrate was confirmed. Upon treatments with Ca2+ this was not observed, suggesting the participation of mitochondriat endonucleases in the mechanism of breakage, despite the increase in ROS production due to MTP opening. In this work, evidence was provided that the mtDNA injury associated with oxidative stress situations was closely related to the loss of inner membrane integrity, independently of the mechanism by which the permeabilization was induced.

Original languageEnglish
JournalFASEB Journal
Issue number9
Publication statusPublished - 1997

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology
  • Genetics
  • Molecular Biology
  • Biotechnology


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