Iron(II) induces changes in the conformation of mammalian mitochondrial DNA resulting in a reduction of its transcriptional rate.
Living isolated mitochondria incubated with iron(II) show a major alteration in mitochondrial DNA (mtDNA) conformational forms as assessed by Southern blot analysis of undigested mtDNA. In the presence of iron(II), form I is transformed into form III in a dose-dependent manner. This alteration in mtDNA conformation shows a strong correlation with a decrease in the mtDNA transcription rate (r=0.965, P < 0.002), suggesting that iron(II) load results in double-strand breaks and unwinding of mtDNA, which, in turn, is unable to maintain its normal transcriptional rate.
Asín
J
J
Centre d'Investigacions en Bioquimica i Biologia Molecular, Hospitals Vall d'Hebron, Barcelona, Spain.
Pérez-Martos
A
A
Fernández-Silva
P
P
Montoya
J
J
Andreu
A L
AL
D000818:Animals; D002413:Cations, Divalent; D004272:DNA, Mitochondrial / Q000737:chemistry; D005296:Ferrous Compounds / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D008297:Male; D008322:Mammals; D008929:Mitochondria, Heart; D009690:Nucleic Acid Conformation; D051381:Rats; D017208:Rats, Wistar; D014158:Transcription, Genetic
D002413:Cations, Divalent; D004272:DNA, Mitochondrial; D005296:Ferrous Compounds; D007501:Iron