Subcellular compartmentalization of NAD+ and its role in cancer: A sereNADe of metabolic melodies

Yi Zhu, Jiaqi Liu, Joun Park, Priyamvada Rai, Rong G. Zhai

Research output: Contribution to journalReview articlepeer-review

17 Scopus citations


Nicotinamide adenine dinucleotide (NAD+) is an essential biomolecule involved in many critical processes. Its role as both a driver of energy production and a signaling molecule underscores its importance in health and disease. NAD+ signaling impacts multiple processes that are dysregulated in cancer, including DNA repair, cell proliferation, differentiation, redox regulation, and oxidative stress. Distribution of NAD+ is highly compartmentalized, with each subcellular NAD+ pool differentially regulated and preferentially involved in distinct NAD+-dependent signaling or metabolic events. Emerging evidence suggests that targeting NAD+ metabolism is likely to repress many specific mechanisms underlying tumor development and progression, including proliferation, survival, metabolic adaptations, invasive capabilities, heterotypic interactions with the tumor microenvironment, and stress response including notably DNA maintenance and repair. Here we provide a comprehensive overview of how compartmentalized NAD+ metabolism in mitochondria, nucleus, cytosol, and extracellular space impacts cancer formation and progression, along with a discussion of the therapeutic potential of NAD+-targeting drugs in cancer.

Original languageEnglish (US)
Pages (from-to)27-41
Number of pages15
JournalPharmacology and Therapeutics
StatePublished - Aug 2019
Externally publishedYes


  • CD38
  • NAD
  • PARP
  • SIRT

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


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