Published February 8, 2008 | Version v1
Journal article

Identification of poly(ADP-ribose) polymerase-1 as the OXPHOS-generated ATP sensor of nuclei of animal cells

  • 1. Department of Cellular and Molecular Pharmacology, University of California San Francisco, School of Medicine, San Francisco, CA 94143 (United States)
  • 2. UCSF Helen Diller Family Comprehensive Cancer Center, Department of Anatomy, University of California, School of Medicine, San Francisco Medical Center, San Francisco, CA 94143 (United States)
  • 3. Department of Medical Biochemistry, Semmelweis University, Budapest (Hungary)

Description

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

Availability note (English)

Available from http://dx.doi.org/10.1016/j.bbrc.2007.12.004

Additional details

Identifiers

DOI
10.1016/j.bbrc.2007.12.004;
PII
S0006-291X(07)02622-8;

Publishing Information

Journal Title
Biochemical and Biophysical Research Communications
Journal Volume
366
Journal Issue
2
Journal Page Range
p. 568-573
ISSN
0006-291X
CODEN
BBRCA9

Optional Information

Copyright
Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.