Mitochondrial dysfunction and mitochondrial DNA mutations in atherosclerotic complications in diabetes
Dimitry A Chistiakov1, Igor A Sobenin, Yuri V Bobryshev
1Dimitry A Chistiakov, Igor A Sobenin, Department of Medical Nanobiotechnology, Pirogov Russian State Medical University, 117997 Moscow, Russia.
Abstract:
Mitochondrial DNA (mtDNA) is particularly prone to oxidation due to the lack of histones and a deficient mismatch repair system. This explains an increased mutation rate of mtDNA that results in heteroplasmy, e.g., the coexistence of the mutant and wild-type mtDNA molecules within the same mitochondrion. In diabetes mellitus, glycotoxicity, advanced oxidative stress, collagen cross-linking, and accumulation of lipid peroxides in foam macrophage cells and arterial wall cells may significantly decrease the mutation threshold required for mitochondrial dysfunction, which in turn further contributes to the oxidative damage of the diabetic vascular wall, endothelial dysfunction, and atherosclerosis.
Insights
Mitochondrial DNA (mtDNA) mutations increase due to oxidative stress, common in diabetes. This leads to mitochondrial dysfunction, damaging blood vessels and promoting atherosclerosis.
Area of Science:
- Biochemistry
- Genetics
- Pathology
Background:
- Mitochondrial DNA (mtDNA) is susceptible to oxidative damage due to limited protective mechanisms.
- Oxidative stress and impaired DNA repair in mitochondria lead to mutations and heteroplasmy.
Purpose of the Study:
- To explore the role of mitochondrial DNA oxidation and mutations in the vascular complications of diabetes mellitus.
Main Methods:
- The study discusses the biochemical and cellular mechanisms underlying mtDNA damage in diabetes.
- It reviews existing literature on oxidative stress, glycotoxicity, and their impact on mitochondrial function.
Main Results:
- Diabetes mellitus exacerbates mtDNA oxidation through glycotoxicity and lipid peroxidation.
- This oxidative stress lowers the threshold for mitochondrial dysfunction, increasing mutation rates.
- Accumulation of mtDNA mutations contributes to vascular wall damage and endothelial dysfunction.
Conclusions:
- Oxidative stress in diabetes significantly impacts mtDNA integrity, promoting mutations.
- Mitochondrial dysfunction is a key factor in the development of diabetic vascular complications, including atherosclerosis.
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