Mitochondrial reactive oxygen species cause major oxidative mitochondrial DNA damages and repair pathways
Zhenqiu Huang1, Yinnan Chen, Yanmin Zhang
1Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Abstract:
Mitochondria-derived reactive oxygen species (mROS) are produced at a variety of sites and affect the function of bio-molecules. The anti-oxidant system from both mitochondria and cytosol tightly coordinate to maintain the redox balance of cells and reduce damage from mROS. Mitochondrial DNA (mtDNA) are highly susceptible to mROS, and are easily oxidized to accumulate DNA modifications. Frequent oxidative damages in mtDNA have been associated with neurological degeneration, inflammasomes, tumorigenesis, and malignant progression. Among mitochondrial DNA repair pathways, the base excision repair pathway has been extensively characterized to remove some of oxidative damages in mtDNA as efficiently as the nuclear base excision repair. The implications of other pathways remain unclear. This review focuses on: (i) Sources of mROS and the antioxidant system to balance redox status; (ii) major mtDNA lesions or damages from mROS-mediated oxidation and the reported repair pathways or repairing factors; (iii) cellular response of oxidized mtDNA and methods to identify oxidatively generated DNA modifications in pathological conditions. DNA damages caused by mROS have been increasingly implicated in diseases and aging, and thus we critically discuss methods of the oxidative modifications evaluation and the complexity of non-canonical DNA repair pathways in mitochondria.
Insights
Mitochondria-derived reactive oxygen species (mROS) cause DNA damage, impacting cell health and disease. This review explores mROS sources, mtDNA damage, and repair mechanisms, highlighting their role in aging and pathology.
Area of Science:
- Cellular Biology
- Molecular Biology
- Biochemistry
Background:
- Mitochondria-derived reactive oxygen species (mROS) impact cellular function and redox balance.
- Mitochondrial DNA (mtDNA) is vulnerable to mROS, leading to oxidative damage linked to diseases like neurodegeneration and cancer.
- Cellular antioxidant systems in mitochondria and cytosol maintain redox homeostasis.
Purpose of the Study:
- To review the sources of mROS and cellular antioxidant systems.
- To identify major mtDNA lesions caused by mROS and their repair pathways.
- To discuss cellular responses to oxidized mtDNA and methods for detecting oxidative DNA modifications in disease.
Main Methods:
- Literature review of mROS generation, antioxidant systems, mtDNA damage, and repair mechanisms.
- Analysis of studies on cellular responses to oxidized mtDNA.
- Evaluation of methods for identifying oxidative DNA modifications.
Main Results:
- mROS are significant contributors to cellular oxidative stress and mtDNA damage.
- Base excision repair is a key pathway for repairing oxidative mtDNA lesions, though other pathways' roles are less understood.
- Oxidative mtDNA damage is implicated in various pathologies and aging.
Conclusions:
- Understanding mROS, mtDNA damage, and repair is crucial for addressing diseases linked to oxidative stress.
- Further research into non-canonical mitochondrial DNA repair pathways is needed.
- Accurate evaluation of oxidative modifications is essential for pathological studies.
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