NAD+ plays essential roles in cellular energy homoeostasis and redox state, functioning as a cofactor along the glycolysis and citric acid cycle pathways. Recent discoveries indicated that, through the NAD+-consuming enzymes, this molecule may also be involved in many other cellular and biological outcomes such as chromatin remodelling, gene transcription, genomic integrity, cell division, calcium signalling, circadian clock and pluripotency. Poly(ADP-ribose) polymerase 1 (PARP1) is such an enzyme and dysfunctional PARP1 has been linked with the onset and development of various human diseases, including cancer, aging, traumatic brain injury, atherosclerosis, diabetes and inflammation. In the present study, we showed that overexpressed acyl-CoA-binding domain containing 3 (ACBD3), a Golgi-bound protein, significantly reduced cellular NAD+ content via enhancing PARP1's polymerase activity and enhancing auto-modification of the enzyme in a DNA damage-independent manner. We identified that extracellular signal-regulated kinase (ERK)1/2 as well as de novo fatty acid biosynthesis pathways are involved in ACBD3-mediated activation of PARP1. Importantly, oxidative stress-induced PARP1 activation is greatly attenuated by knocking down the ACBD3 gene. Taken together, these findings suggest that ACBD3 has prominent impacts on cellular NAD+ metabolism via regulating PARP1 activation-dependent auto-modification and thus cell metabolism and function.
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Research Article|
July 06 2015
Acyl-CoA-binding domain containing 3 modulates NAD+ metabolism through activating poly(ADP-ribose) polymerase 1
Yong Chen;
Yong Chen
*Department of Psychiatry, Center for Neurobiology and Behavior, The Perlman School of Medicine at University of Pennsylvania, Philadelphia, PA 19104, U.S.A.
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Sookhee Bang;
Sookhee Bang
*Department of Psychiatry, Center for Neurobiology and Behavior, The Perlman School of Medicine at University of Pennsylvania, Philadelphia, PA 19104, U.S.A.
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Soohyun Park;
Soohyun Park
*Department of Psychiatry, Center for Neurobiology and Behavior, The Perlman School of Medicine at University of Pennsylvania, Philadelphia, PA 19104, U.S.A.
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Hanyuan Shi;
Hanyuan Shi
*Department of Psychiatry, Center for Neurobiology and Behavior, The Perlman School of Medicine at University of Pennsylvania, Philadelphia, PA 19104, U.S.A.
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Sangwon F. Kim
Sangwon F. Kim
1
*Department of Psychiatry, Center for Neurobiology and Behavior, The Perlman School of Medicine at University of Pennsylvania, Philadelphia, PA 19104, U.S.A.
†Department of Systems Pharmacology and Translational Therapeutics, Center for Neurobiology and Behavior, The Perlman School of Medicine at University of Pennsylvania, Philadelphia, PA 19104, U.S.A.
1To whom correspondence should be addressed (email [email protected]).
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Publisher: Portland Press Ltd
Received:
December 08 2014
Revision Received:
April 22 2015
Accepted:
May 05 2015
Accepted Manuscript online:
May 05 2015
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2015 Authors; published by Portland Press Limited
2015
Biochem J (2015) 469 (2): 189–198.
Article history
Received:
December 08 2014
Revision Received:
April 22 2015
Accepted:
May 05 2015
Accepted Manuscript online:
May 05 2015
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Citation
Yong Chen, Sookhee Bang, Soohyun Park, Hanyuan Shi, Sangwon F. Kim; Acyl-CoA-binding domain containing 3 modulates NAD+ metabolism through activating poly(ADP-ribose) polymerase 1. Biochem J 15 July 2015; 469 (2): 189–198. doi: https://doi.org/10.1042/BJ20141487
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