Age-related Fragmentation of Mitochondrial DNA Associated with Oxygen Damage
Committee on Biotechnology PAS ; Institute of Bioorganic Chemistry PAS
In normal human hearts, a progressive age-related fragmentation of mitochondrial (mt) DNAinto various-sized deleted (A) mtDNA up to 358 types was documented by a novel total-detectionsystem for deletions. The AmtDNA lacking replication origin(s), minicircles, accumulated up to280 types out of the 358, suggesting a yet unknown replication mechanism in human. Wild-typemtDNA decreased linearly down to 11% of the total with age negatively correlated with AmtDNAand oxidized nucleoside, 8-hydroxy-deoxyguanosine. A remarkable mirror image observed inAmtDNA size distribution as well implies that random hydroxyl-radical attacks resulted in doublestrand break and rejoining of mtDNA as a preferable mechanism to form various AmtDNA ofclosed circular duplex. In the patients with mitochondrial cardiomyopathy, similar fragmentationand oxidative damage in mtDNA was documented at their age 7 to 19 equivalent to the normalsubjects of age over 80. Exposure of a cultured cell line under oxygen stress, 95% oxygen, coldmimic these changes in mtDNA* within 3 days leading an apoptotic cell death, whereas mtDNAlacking cells are relatively immune. These facts support the ‘redox mechanism of ageing’.
Biotechnologia, vol.35, 4 (1996)-.
0860-7796 ; oai:rcin.org.pl:146571 ; IChB B-31
Library of Institute of Bioorganic Chemistry PAS
Creative Commons Attribution BY-SA 4.0 license
Institute of Bioorganic Chemistry of the Polish Academy of Science
Institute of Bioorganic Chemistry of the Polish Academy of Science
Nov 9, 2020
Nov 9, 2020
31
https://rcin.org.pl/ichb/publication/182249
Edition name | Date |
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Age-related Fragmentation of Mitochondrial DNA Associated with Oxygen Damage | Nov 9, 2020 |
Borkowska, Bożenna
Ziółkowski, Piotr Babula- Skowrońska, Danuta Kaczmarek, Małgorzata Cieśla, Agata Sadowski, Jan