title: Endogenous mitochondrial oxidative stress in MnSOD-deficient mouse embryonic fibroblasts promotes mitochondrial DNA glycation.
abstract: The accumulation of somatic mutations in mitochondrial DNA (mtDNA) induced by reactive oxygen species (ROS) is regarded as a major contributor to aging and age-related degenerative diseases. ROS have also been shown to facilitate the formation of certain advanced glycation end-products (AGEs) in proteins and DNA and N(2)-carboxyethyl-2'-deoxyguanosine (CEdG) has been identified as a major DNA-bound AGE. Therefore, the influence of mitochondrial ROS on the glycation of mtDNA was investigated in primary embryonic fibroblasts derived from mutant mice (Sod2(-/+)) deficient in the mitochondrial antioxidant enzyme manganese superoxide dismutase. In Sod2(-/+) fibroblasts vs wild-type fibroblasts, the CEdG content of mtDNA was increased from 1.90 ± 1.39 to 17.14 ± 6.60 pg/μg DNA (p<0.001). On the other hand, the CEdG content of nuclear DNA did not differ between Sod2(+/+) and Sod2(-/+) cells. Similarly, cytosolic proteins did not show any difference in advanced glycation end-products or protein carbonyl contents between Sod2(+/+) and Sod2(-/+). Taken together, the data suggest that mitochondrial oxidative stress specifically promotes glycation of mtDNA and does not affect nuclear DNA or cytosolic proteins. Because DNA glycation can change DNA integrity and gene functions, glycation of mtDNA may play an important role in the decline of mitochondrial functions.
authors.affiliation: Department of Chemistry and Pharmacy, Food Chemistry, Emil Fischer Center, Friedrich-Alexander University Erlangen-Nuremberg, D-91052 Erlangen, Germany.
authors.forename: Viola
authors.initials: V
authors.lastname: Breyer
authors.forename: Ingrid
authors.initials: I
authors.lastname: Weigel
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Huang
authors.forename: Monika
authors.initials: M
authors.lastname: Pischetsrieder
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004272:DNA, Mitochondrial / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D004622:Embryo, Mammalian / Q000201:enzymology*; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000201:enzymology; D005947:Glucose / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial; D013482:Superoxide Dismutase; D005947:Glucose