A Ca2+-induced mitochondrial permeability transition causes complete release of rat liver endonuclease G activity from its exclusive location within the mitochondrial intermembrane space. Identification of a novel endo-exonuclease activity residing within the mitochondrial matrix.
Endonuclease G, a protein historically thought to be involved in mitochondrial DNA (mtDNA) replication, repair, recombination and degradation, has recently been reported to be involved in nuclear DNA degradation during the apoptotic process. As a result, its involvement in mtDNA homeostasis has been called into question and has necessitated detailed analyses of its precise location within the mitochondrion. Data is presented localizing rat liver endonuclease G activity exclusively to the mitochondrial intermembrane space with no activity associated with either the interior face of the inner mitochondrial membrane or with the mitochondrial matrix. Additionally, it is shown that endonuclease G can be selectively released from the mitochondrion via induction of a Ca2+-induced mitochondrial permeability transition and that, upon its release, a further nuclease activity loosely associated with the interior face of the inner mitochondrial membrane and distinct in its properties from that of endonuclease G can be detected.
Davies
Adrian M
AM
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Hershman
Stuart
S
Stabley
Gabriel J
GJ
Hoek
Jan B
JB
Peterson
Jason
J
Cahill
Alan
A
D000818:Animals; D001665:Binding Sites; D015153:Blotting, Western; D002118:Calcium / Q000494:pharmacology*; D004272:DNA, Mitochondrial / Q000378:metabolism; D004278:DNA, Superhelical / Q000378:metabolism; D003851:Deoxyribonucleases / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000378:metabolism*; D007425:Intracellular Membranes / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D010539:Permeability / Q000187:drug effects; D010957:Plasmids / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D004272:DNA, Mitochondrial; D004278:DNA, Superhelical; D008565:Membrane Proteins; D003851:Deoxyribonucleases; D004706:Endodeoxyribonucleases; C052391:endonuclease G; D002118:Calcium