Mitochondrial DNA repair pathways

Croteau, Deborah L.; Stierum, Rob; Bohr, Vilhelm A.

doi:10.1016/s0921-8777(99)00025-7

Cited by 215 publications

(118 citation statements)

References 69 publications

Supporting

Mentioning

110

Contrasting

Unclassified

Order By: Relevance

“…These include mitochondrial DNA repair (19), apoptosis, and immune surveillance that eliminates cells with mutated mitochondrial DNA. Mutations that cause uncoupling or interruption of the electron transfer chain often result in increased ROS production, thus triggering cytochrome c release and cellular apoptosis (20,21).…”

Section: Resultsmentioning

confidence: 99%

Role of MHC Class I in Immune Surveillance of Mitochondrial DNA Integrity

Wang

Roifman

et al. 2003

The Journal of Immunology

View full text Add to dashboard Cite

Mitochondrial DNA is subject to increased rates of mutations due to its proximity to the source of reactive oxygen species. Here we show that increased MHC class I (MHC I) expression serves to alert the immune system to cells with mitochondrial mutations. MHC I is overexpressed in fibroblasts with mitochondrial dysfunction from patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes and in lymphocytes from purine nucleoside phosphorylase-deficient immune-deficient mice with mitochondrial DNA deletions. Consistent with a role of MHC I in the elimination of cells containing mitochondrial DNA mutations, mice deficient in MHC I accumulate mitochondrial DNA deletions in various tissues. These observations in both mice and humans suggest a role for the immune system in preventing reversion of mitochondrial DNA back into a parasitic state following deleterious mutations affecting mitochondrial oxidative phosphorylation.

show abstract

Section: Resultsmentioning

confidence: 99%

Role of MHC Class I in Immune Surveillance of Mitochondrial DNA Integrity

Wang

Roifman

et al. 2003

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…The mitochondrial genome is more susceptible to oxidative damage than nDNA due to the absence of histone, incomplete DNA repair capacity and proximity to the mitochondrial respiratory chain, which is the main intracellular source of reactive oxygen species. 20,35,36 Previous studies on acute ethanol intoxication in mice reported a rapid fall of hepatic mtDNA levels which could be, at least in part, related to lipid peroxidation. [37][38][39] Thus both ethanol and CCl 4 induce lipid peroxidation and mtDNA depletion 2 or 3 h following their administration.…”

Section: Discussionmentioning

confidence: 99%

Carbon tetrachloride-mediated lipid peroxidation induces early mitochondrial alterations in mouse liver

Knockaert

Berson

Ribault

et al. 2012

Laboratory Investigation

109

View full text Add to dashboard Cite

Although carbon tetrachloride (CCl 4 )-induced acute and chronic hepatotoxicity have been extensively studied, little is known about the very early in vivo effects of this organic solvent on oxidative stress and mitochondrial function. In this study, mice were treated with CCl 4 (1.5 ml/kg ie 2.38 g/kg) and parameters related to liver damage, lipid peroxidation, stress/defense and mitochondria were studied 3 h later. Some CCl 4 -intoxicated mice were also pretreated with the cytochrome P450 2E1 inhibitor diethyldithiocarbamate or the antioxidants Trolox C and dehydroepiandrosterone. CCl 4 induced a moderate elevation of aminotransferases, swelling of centrilobular hepatocytes, lipid peroxidation, reduction of cytochrome P4502E1 mRNA levels and a massive increase in mRNA expression of heme oxygenase-1 and heat shock protein 70. Moreover, CCl 4 intoxication induced a severe decrease of mitochondrial respiratory chain complex IV activity, mitochondrial DNA depletion and damage as well as ultrastructural alterations. Whereas DDTC totally or partially prevented all these hepatic toxic events, both antioxidants protected only against liver lipid peroxidation and mitochondrial damage. Taken together, our results suggest that lipid peroxidation is primarily implicated in CCl 4 -induced early mitochondrial injury. However, lipid peroxidation-independent mechanisms seem to be involved in CCl 4 -induced early hepatocyte swelling and changes in expression of stress/defense-related genes. Antioxidant therapy may not be an efficient strategy to block early liver damage after CCl 4 intoxication.

show abstract

“…Therefore, every point mutation, or deletion, has the capacity to affect the mitochondrial function of cellular respiration support. MtDNA also lacks the protection of histones or DNA binding proteins (Shoffner et al, 1993) and is believed to have only a very basic repair mechanism (Croteau et al, 1999). Bohr and Dianov have reported that this mechanism can repair excision and bases caused by oxidative insult (Bohr and Dianov, 1999).…”

Section: Introductionmentioning

confidence: 99%

A comparison of mitochondrial and nuclear DNA status in testicular sperm from fertile men and those with obstructive azoospermia

O’Connell

McClure²,

Lewis

2002

Human Reproduction

View full text Add to dashboard Cite

BACKGROUND: Mitochondria are vital to sperm as their motility powerhouses. They are also the only animal organelles with their own unique genome; encoding subunits for the complexes required for the electron transfer chain. METHODS: A modified long PCR technique was used to study mitochondrial DNA (mtDNA) in ejaculated and testicular sperm samples from fertile men undergoing vasectomy (n ⍧ 11) and testicular sperm from men with obstructive azoospermia (n ⍧ 25). Nuclear DNA (nDNA) fragmentation was measured by an alkaline gel electrophoresis (comet) assay. RESULTS: Wild-type mtDNA was detected in only 60% of fertile men's testicular sperm, 50% of their ejaculated sperm and 46% of testicular sperm from men with obstructive azoospermia. The incidence of mitochondrial deletions in testicular sperm of fertile and infertile men was not significantly different, but the mean size of the deletions was significantly less in testicular sperm from fertile men compared with men with obstructive azoospermia (P < 0.02). NDNA fragmentation in testicular sperm from fertile men and men with obstructive azoospermia was not significantly different. CONCLUSION: Multiple mtDNA deletions are common in testicular and ejaculated sperm from both fertile and infertile men. However, in males with obstructive azoospermia, the mtDNA deletions in testicular sperm are of a larger scale.Key words: human sperm/male infertility/mitochondrial and nuclear DNA/obstructive azoospermia/ROS

show abstract

Mitochondrial DNA repair pathways

Cited by 215 publications

References 69 publications

Role of MHC Class I in Immune Surveillance of Mitochondrial DNA Integrity

Role of MHC Class I in Immune Surveillance of Mitochondrial DNA Integrity

Carbon tetrachloride-mediated lipid peroxidation induces early mitochondrial alterations in mouse liver

A comparison of mitochondrial and nuclear DNA status in testicular sperm from fertile men and those with obstructive azoospermia

Contact Info

Product

Resources

About