Reactive oxygen and DNA damage in mitochondria

https://doi.org/10.1016/0921-8734(92)90029-OGet rights and content

Abstract

During the last decade the importance of reactive oxygen species as major contributors to various types of cancer, heart diseases, cataracts, Parkinson's and other degenerative diseases that come with age, and to natural aging has become apparent. Mitochondria are the most important intracellular source of reactive oxygen. Mitochondrial DNA is heavily damaged by reactive oxygen at the bases, as indicated by the high steady-state level of 8-hydroxydeoxyguanosine, the presence of which causes mispairing and point mutations. Mitochondrial DNA is also oxidatively fragmented to a certain extent. Conceivably, such fragmentation relates to deletions found in mitochondrial DNA. Point mutations and deletions have recently been shown to be etiologically linked to several human diseases and natural aging. Future studies should address the causal relationship between mitochondrial dysfunction, production of reactive oxygen species, and aging.

References (89)

  • B. Halliwell et al.

    DNA damage by oxygen-derived species. Its mechanism and measurement in mammalian systems

    FEBS Lett.

    (1991)
  • K. Hattori et al.

    Age-dependent increase in deleted mitochondrial DNA in the human heart: possible contributory factor in presbycardia

    Am. Heart J.

    (1991)
  • M. Hayakawa et al.

    Age-associated accumulation to 8-hydroxyguanosine in mitochondrial DNA of human diaphragm

    Biochem. Biophys. Res. Commun.

    (1991)
  • A.M. Hruszkewycz et al.

    The 8-hydroxyguanine content of isolated mitochondria increases with lipid peroxidation

    Mutation Res.

    (1990)
  • S. Ikebe et al.

    Increase of deleted mitochondrial DNA in the striatum in Parkinson's disease and senescence

    Biochem. Biophys. Res. Commun.

    (1990)
  • E.S. Lander et al.

    Mitochondrial diseases: gene mapping and gene therapy

    Cell

    (1990)
  • A.W. Linnane et al.

    Mitochondrial DNA mutations as an important contributor to aging and degenerative diseases

    Lancet

    (1989)
  • V.M. Mann et al.

    Quantitation of a mitochondrial DNA deletion in Parkinson's disease

    FEBS Lett.

    (1992)
  • J. Miquel

    An integrated theory of aging as the result of mitochondrial-DNA mutation in differentiated cells

    Arch. Gerontol. Geriatr.

    (1991)
  • J. Miquel et al.

    Mitochondrial role in cell aging

    Exp. Gerontol.

    (1980)
  • J. Müller-Höcker

    Cytochrome oxidase deficient fibres in the limb muscle and diaphragm of man without muscular disease: an age-related alteration

    J. Neurol. Sci.

    (1990)
  • H. Nohl et al.

    2,3,7,8-Tetrachlorodibenzo-p-dioxin induces oxygen activation associated with cell respiration

    Free Radical Biol. Med.

    (1989)
  • T. Ozawa et al.

    Quantitative determination of deleted mitochondrial DNA relative to normal DNA in parkinsonian striatum by a kinetic PCR analysis

    Biochem. Biophys. Res. Commun.

    (1990)
  • L. Piko et al.

    Studies of sequence heterogeneity of mitochondrial DNA from rat and mouse tissue: evidence for an increased frequency of deletions/additions with aging

    Mech. Ageing Dev.

    (1988)
  • C. Richter

    Do mitochondrial DNA fragments promote cancer and aging?

    FEBS Lett.

    (1988)
  • M.S. Satoh et al.

    Enzymatic removal of O6-ethylguanine from mitochondrial DNA in rat tissue exposed to N-ethyl-N-nitrosourea in vivo

    J. Biol. Chem.

    (1988)
  • M. Sawada et al.

    Changes in superoxide radical formation in the brain, heart and liver during tthe lifetime of the rat

    Mech. Ageing Dev.

    (1987)
  • K. Schulze-Osthoff et al.

    Cytotoxic activity of tumor necrosis factor is mediated by early damage of mitochondrial functions

    J. Biol. Chem.

    (1992)
  • R.S. Sohal

    Hydrogen peroxide production by mitochondria may be a biomarker of aging

    Mech. Ageing Dev.

    (1991)
  • R.S. Sohal et al.

    Age-related changes in antioxidant enzymes and prooxidant generation in tissues of the rat with special reference to parameters in two insect species

    Free Radical Biol. Med.

    (1990)
  • S. Sugiyama et al.

    Quantitative analysis of age-associated accumulation of mitochondrial DNA with deletion in human heart

    Biochem. Biophys. Res. Commun.

    (1991)
  • A.E. Tomkinson et al.

    Mitochondrial endonuclease activities specific for apurinic/apyrimidinic sites in DNA from mouse cells

    J. Biol. Chem.

    (1988)
  • I. Trounce et al.

    Decline in skeletal muscle mitochondrial respiratory chain function: possible factor in aging

    Lancet

    (1989)
  • T. Yen et al.

    Ageing-associated 5 kb deletion in human liver mitochondrial DNA

    Biochem. Biophys. Res. Commun.

    (1991)
  • B.N. Ames

    Dietary carcinogens and anticarcinogens. Oxygen radicals and degenerative diseases

    Science

    (1983)
  • J.M. Backer et al.

    Mitochondrial DNA is a major cellular target for a dihydrodiol-epoxide derivative of benzo[α]pyrene

    Science

    (1980)
  • W.M. Brown et al.

    Rapid evolution of animal mitochondrial DNA

  • E. Cadenas

    Biochemistry of oxygen toxicity

    Annu. Rev. Biochem.

    (1989)
  • B. Chance et al.

    Hydroperoxide metabolism in mammalian organs

    Physiol. Rev.

    (1979)
  • M.W.J. Cleeter et al.

    Irreversible inhibition of mitochondrial complex I by 1-methyl-4-phenylpyridinium: evidence for free radical involvement

    J. Neurochem.

    (1992)
  • G.A. Cortopassi et al.

    Detection of specific mitochondrial DNA deletions in tissues of older humans

    Nucleic Acids Res.

    (1990)
  • C. De Giorgi et al.

    Mitochondrial genome in animal cells. Structure, organization, and evolution

    Cell Biophys.

    (1989)
  • J.E. Fleming et al.

    Is cell aging caused by respiration-dependent injury to the mitochondrial genome?

    Gerontology

    (1982)
  • C.G. Fraga et al.

    Oxidative damage to DNA during aging: 8-hydroxy-2′-deoxyguanosine in rat organ DNA and urine

  • Cited by (209)

    • Oxidative stress and DNA damage in critically ill patients with sepsis

      2023, Mutation Research - Genetic Toxicology and Environmental Mutagenesis
    • Fundamental Biological Features of Spaceflight: Advancing the Field to Enable Deep-Space Exploration

      2020, Cell
      Citation Excerpt :

      Amplification of mitochondrial ROS by ionizing radiation leads to mutations in mitochondrial DNA and subsequent disturbance of the expression of critical proteins for mitochondrial and cellular functions (Azzam et al., 2012). Notably, oxidative damage in mitochondrial DNA (mtDNA) is several-fold higher than in nuclear DNA (Richter, 1992), which can be due to the lack of protective histone proteins and less-efficient DNA repair mechanisms for mtDNA (Wiseman and Halliwell, 1996). In addition, a significant decrease in the ratio between mtDNA to nuclear DNA was observed between pre- and post-flight astronaut hair samples, as well as a significant decrease in the expression of genes related to oxidative stress (Indo et al., 2016), and more in-flight mtDNA and mtRNA were observed in peripheral blood during NASA’s first year-long mission (Garrett-Bakelman et al., 2019).

    • Astrocyte elevated gene-1 (AEG-1) and the A(E)Ging HIV/AIDS-HAND

      2017, Progress in Neurobiology
      Citation Excerpt :

      Oxidative damage affects mitochondrial DNA transcription and disrupts mitochondrial function that in turn enhances ROS production (Cui et al., 2012). Higher rates of oxidative stress-induced DNA damage are seen in mitochondrial DNA as compared to nuclear DNA, suggesting that mitochondrial DNA is more susceptible to oxidative stress (Richter, 1992; Santos et al., 2002). Mitochondria play a significant role in apoptosis and mitochondrial redox imbalance could enhance apoptotic cell death and aging.

    View all citing articles on Scopus
    View full text