Acyl-CoA-binding domain containing 3 modulates NAD+ metabolism through activating poly(ADP-ribose) polymerase 1

Yong Chen, Sookhee Bang, Soohyun Park, Hanyuan Shi, Sangwon F. Kim

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)189-198
Number of pages10
JournalBiochemical Journal
Issue number2
StatePublished - Jul 15 2015
Externally publishedYes


  • Acyl-CoA-binding domain containing 3 (ACBD3)
  • Lipid metabolism
  • Nicotinamide adenine dinucleotide (NAD)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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