The permeability transition pore as a pathway for the release of mitochondrial DNA.
This study shows that under oxidative stress DNA from liver mitochondria (mtDNA) can be released through the non-specific permeability transition pore. Pore opening was induced after the addition of Fe2+ and hydrogen peroxide, in the presence of calcium ions. Under these conditions mitochondria undergo large extent swelling, accompanied by the generation of thiobarbituric acid-reactive substances. It was observed that mtDNA was hydrolyzed after the oxidative stress, and it is proposed that some of the fragments were released from the matrix, in such a way that approximately 12% of the total mtDNA remained in the mitochondria. The remaining genetic material was analyzed, after its extraction in an agarose gel. The fragments released were smaller that 1000 bp, by analysis in a native 8% polyacrilamide gel. The presence of cyclosporin A, that inhibited permeability transition, also inhibited mtDNA release by roughly 52%.
García
Noemí
N
Departamento de Bioquímica, Instituto Nacional de Cardiología, Ignacio Chávez, Juan Badiano #1, México DF 014080, Mexico. ngarciar@salud.gob.mx
García
José J
JJ
Correa
Francisco
F
Chávez
Edmundo
E
D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D016572:Cyclosporine / Q000494:pharmacology; D004272:DNA, Mitochondrial / Q000378:metabolism*; D004587:Electrophoresis, Agar Gel; D006861:Hydrogen Peroxide / Q000633:toxicity; D007501:Iron / Q000633:toxicity; D015227:Lipid Peroxidation / Q000187:drug effects; D008930:Mitochondria, Liver / Q000378:metabolism*; D008933:Mitochondrial Swelling / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010539:Permeability; D051381:Rats; D013053:Spectrophotometry; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D004272:DNA, Mitochondrial; D017392:Thiobarbituric Acid Reactive Substances; D016572:Cyclosporine; D006861:Hydrogen Peroxide; D007501:Iron; D000263:Adenylate Kinase