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- Title
Is There Still Any Role for Oxidative Stress in Mitochondrial DNA-Dependent Aging?
- Authors
Zsurka, Gábor; Peeva, Viktoriya; Kotlyar, Alexander; Kunz, Wolfram S.
- Abstract
Recent deep sequencing data has provided compelling evidence that the spectrum of somatic point mutations in mitochondrial DNA (mtDNA) in aging tissues lacks G > T transversion mutations. This fact cannot, however, be used as an argument for the missing contribution of reactive oxygen species (ROS) to mitochondria-related aging because it is probably caused by the nucleotide selectivity of mitochondrial DNA polymerase γ (POLG). In contrast to point mutations, the age-dependent accumulation of mitochondrial DNA deletions is, in light of recent experimental data, still explainable by the segregation of mutant molecules generated by the direct mutagenic effects of ROS (in particular, of HO· radicals formed from H2O2 by a Fenton reaction). The source of ROS remains controversial, because the mitochondrial contribution to tissue ROS production is probably lower than previously thought. Importantly, in the discussion about the potential role of oxidative stress in mitochondria-dependent aging, ROS generated by inflammation-linked processes and the distribution of free iron also require careful consideration.
- Subjects
MITOCHONDRIAL DNA; OXIDATIVE stress; HABER-Weiss reaction; REACTIVE oxygen species; NUCLEOTIDES
- Publication
Genes, 2018, Vol 9, Issue 4, p175
- ISSN
2073-4425
- Publication type
Article
- DOI
10.3390/genes9040175