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

Journal Article · Fri Feb 08 04:00:00 EST 2008 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2007.12.004· OSTI ID:21043619

Kun, Ernest ^[1]; Kirsten, Eva; Hakam, Alaeddin ^[1]; Bauer, Pal I ^[1]; Mendeleyev, Jerome ^[1]

---

1. 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)

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.

• OSTI ID: 21043619
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 366; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ADP
ANIMAL CELLS
ATP
BIOSYNTHESIS
CELL NUCLEI
INHIBITION
MITOCHONDRIA
NEOPLASMS
POLYMERASES
RIBOSE
TRIOCTYLPHOSPHINE OXIDE