title: Identification of poly(ADP-ribose) polymerase-1 as the OXPHOS-generated ATP sensor of nuclei of animal cells.
abstract: Our results show that in the intact normal animal cell mitochondrial ATP is directly connected to nuclear PARP-1 by way of a specific adenylate kinase enzymatic path. This mechanism is demonstrated in two models: (a) by its inhibition with a specific inhibitor of adenylate kinase, and (b) by disruption of ATP synthesis through uncoupling of OXPHOS. In each instance the de-inhibited PARP-1 is quantitatively determined by enzyme kinetics. The nuclear binding site of PARP-1 is Topo I, and is identified as a critical "switchpoint" indicating the nuclear element that connects OXPHOS with mRNA synthesis in real time. The mitochondrial-nuclear PARP-1 pathway is not operative in cancer cells.
authors: UCSF Helen Diller Family Comprehensive Cancer Center, Department of Anatomy, University of California, School of Medicine, San Francisco Medical Center, San Francisco, CA 94143, USA.
authors: Ernest
authors: E
authors: Kun
authors: Eva
authors: E
authors: Kirsten
authors: Alaeddin
authors: A
authors: Hakam
authors: Pal I
authors: PI
authors: Bauer
authors: Jerome
authors: J
authors: Mendeleyev
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D051381:Rats
chemical_list: D000255:Adenosine Triphosphate; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D004264:DNA Topoisomerases, Type I