Regulation of malignant phenotype and bioenergetics by a π-electron donor-inducible mitochondrial MgATPase.

Int J Mol Med

Department of Anatomy, UCSF Helen Diller Family Comprehensive Cancer Center, University of California, School of Medicine, San Francisco, CA 94143, USA.

Published: February 2011

The recognition of poly ADP-ribose transferase-1 (PARP-1) as an ATP sensor receiving this energy source by way of a specific adenylate kinase ATP wire (AK) from mitochondrial ATP synthase (F0F1), and directly regulating cellular mRNA and DNA synthesis, was the first step towards the identification of an effect by PARP-1 that is of fundamental significance. The molecular target of AK-ATP is Arg 34 of the Zn finger I of PARP-1, which is also a site for cation-π interactions as a target of π-electron donors. We now identify this π-electron receptor site as the second active center of PARP-1 which by interaction with a π-electron donor-inducible MgATPase reversibly controls a malignant vs. non-malignant phenotype through energizing the NADH➝NADP+ transhydrogenase, a reaction which is the metabolic connection of PARP-1 to cell function. The specific enzyme-inducing action of the π-electrons is executed by the PARP-1 -topoisomerase I - DNA complex of the nuclei regulating both the nature and the quantity of cellular enzymes that constitute cell-specific physiology.

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http://dx.doi.org/10.3892/ijmm.2010.567DOI Listing

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