Fragmentation of human heart mitochondrial DNA associated with premature aging

Biochem Biophys Res Commun. 1994 Jul 15;202(1):102-10. doi: 10.1006/bbrc.1994.1899.


Point mutations, oxygen damage and deletions in the heart mitochondrial (mt) DNA of a 19-year-old male patient with premature aging, who died of mitochondrial cardiomyopathy, were comprehensively analyzed. With total base-sequencing, one syn- mutation in the tRNA(Asp) gene and one mit-mutation in the ND3 gene were demonstrated. Using microHPLC/MS, 0.20% of the total deoxyguanosine (dG) were proved to be converted into its hydroxy-radical adduct, 8-hydroxy-dG, of which amount corresponds to that in normal subjects of 78 years old. The total detection system for mtDNA deletions, using 180 kinds of primer pairs, revealed extensive fragmentation of mtDNA; 235 types of deletions existed with various sizes, 97 of which yielded mtDNA minicircles lacking both of the replication origins of light- and heavy-strands. Deleted mtDNA accounted for 84% of the total mtDNA. In a man died from an accident at age 28 having almost the same mtDNA genotype except syn-, 50 types of deleted mtDNA, accounting for 15% of the total, were detected in his heart mtDNA. These results will present a clue to an unidentified mechanism of somatic mtDNA replication and the molecular basis of aging heart.

Publication types

  • Case Reports

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Adult
  • Aging / metabolism*
  • Base Sequence
  • Cardiomyopathies / genetics*
  • Cardiomyopathies / metabolism
  • DNA Damage*
  • DNA, Mitochondrial / chemistry
  • DNA, Mitochondrial / genetics*
  • DNA, Mitochondrial / isolation & purification
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / analysis
  • Heart / growth & development*
  • Humans
  • Male
  • Mitochondria, Heart / metabolism*
  • Molecular Sequence Data
  • Point Mutation*
  • Sequence Deletion*


  • DNA, Mitochondrial
  • 8-Hydroxy-2'-Deoxyguanosine
  • Deoxyguanosine