Mitochondrial endogenous oxidative damage has been overestimated

  title={Mitochondrial endogenous oxidative damage has been overestimated},
  author={Robert Michael Anson and Edgar K. Hudson and Vilhelm A. Bohr},
  journal={The FASEB Journal},
  pages={355 - 360}
The oxidatively induced DNA lesion 8‐oxo‐dG in mitochondrial DNA (mtDNA) is commonly used as a marker for oxidative damage to mitochondria, which in turn is thought to be a fundamental cause of aging. For years, mitochondrial levels of 8‐oxo‐dG were believed to be ~10‐fold higher in mtDNA than in nuclear DNA even in normal, young animals. However, studies in our own and other laboratories have shown that this lesion is efficiently repaired. Also, mutational consequences specific to 8‐oxo‐dG (G… 

Oxidative stress induces degradation of mitochondrial DNA

It is shown that oxidative stress can lead to the degradation of mtDNA and that single strand breaks and abasic sites prevail over mutagenic base lesions in ROS‐damaged mtDNA, suggesting a novel mechanism for the protection of mt DNA against oxidative insults.

Mitochondria, oxidative DNA damage, and aging

Protection from reactive oxygen species (ROS) and from mitochondrial oxidative damage is well known to be necessary to longevity. The relevance of mitochondrial DNA (mtDNA) to aging is suggested by

Mitochondrial DNA oxidative damage and mutagenesis in Saccharomyces cerevisiae.

Methods for quantifying oxidative mtDNA damage and mutagenesis in S. cerevisiae are described, several of which could be applied to the development of similar assays in mammalian cells and tissues.

Gene-specific and mitochondrial repair of oxidative DNA damage.

It is found that damage induction by methylene blue is consistently far greater in the mitochondrion than the nucleus, so advantageously, mitochondrial 8-oxoguanine repair may be studied without mtDNA isolation or preparation, which are processes known to induce DNA damage and skew measurements.

Aging: A mitochondrial DNA perspective, critical analysis and an update.

Issues pertaining to the role of mtDNA in aging are reviewed and exciting new observations from both comparative biology and experimental systems indicate that increased ROS production and oxidative damage to cellular macromolecules, including mtDNA, can be associated with extended longevity.

Does oxidative damage to DNA increase with age?

Dietary restriction was shown to significantly reduce the age-related accumulation of oxo8dG levels in nDNA in all tissues of male B6D23F1 mice and in most tissues ofmale F344 rats, and it was shown that dietary restriction prevented theAge-related increase in oxo 8dG Levels in mtDNA isolated from the livers of both rats and mice.



Endogenous oxidative damage of mtDNA.

Oxidative damage to mitochondrial DNA and its relationship to ageing.

  • C. Richter
  • Biology
    The international journal of biochemistry & cell biology
  • 1995

Oxidative damage to mitochondrial DNA shows marked age‐dependent increases in human brain

Results show for the first time that there is a progressive age‐related accumulation in oxidative damage to DNA in human brain, and that the mtDNA is preferentially affected and it is possible that such damage may contribute to age‐dependent increases in incidence of neurodegenerative diseases.

Normal oxidative damage to mitochondrial and nuclear DNA is extensive.

  • C. RichterJ. ParkB. Ames
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1988
The oxidized base, 8-hydroxydeoxyguanosine (oh8dG), 1 of approximately 20 known radiation damage products, has been assayed in the DNA of rat liver and may be responsible for the observed high mutation rate of mtDNA.

An Oxidative Damage-specific Endonuclease from Rat Liver Mitochondria*

Comparison of mtODE’s activity with other known 8-oxoG glycosylases/lyases and mitochondrial enzymes reveals that this may be a novel protein.

Oxidative damage to mitochondrial DNA is increased in Alzheimer's disease

Results confirm that mitochondrial DNA is particularly sensitive to oxidative damage, and they show that there is increased oxidative damage to DNA in AD, which may contribute to the neurodegenerative process.

Homogenous repair of singlet oxygen-induced DNA damage in differentially transcribed regions and strands of human mitochondrial DNA.

Fpg-sensitive alkali-resistant oxidative base damage was efficiently removed from human mtDNA with no differences in the rate of repair between strands or between two different regions of the genome that differ substantially with regard to transcriptional activity.

Quantification of oxidative DNA modifications in mitochondria.

The data provide evidence that the steady-state levels of oxidative mtDNA modifications are low under physiological conditions, either because reactive oxygen species generated in the mitochondria are instantly inactivated or because of efficient DNA repair processes inside mitochondria.

Detection and quantification of oxidative adducts of mitochondrial DNA.