Biosensor reveals multiple sources for mitochondrial NAD+

Xiaolu A. Cambronne, Melissa L. Stewart, Dongho Kim, Amber M. Jones-Brunette, Rory K. Morgan, David L. Farrens, Michael S. Cohen, Richard H. Goodman

Research output: Contribution to journalArticle

131 Scopus citations

Abstract

Nicotinamide adenine dinucleotide (NAD+) is an essential substrate for sirtuins and poly(adenosine diphosphate-ribose) polymerases (PARPs), which are NAD+-consuming enzymes localized in the nucleus, cytosol, and mitochondria. Fluctuations in NAD+ concentrations within these subcellular compartments are thought to regulate the activity of NAD+-consuming enzymes; however, the challenge in measuring compartmentalized NAD+ in cells has precluded direct evidence for this type of regulation.We describe the development of a genetically encoded fluorescent biosensor for directly monitoring free NAD+ concentrations in subcellular compartments. We found that the concentrations of free NAD+ in the nucleus, cytoplasm, and mitochondria approximate the Michaelis constants for sirtuins and PARPs in their respective compartments. Systematic depletion of enzymes that catalyze the final step of NAD+ biosynthesis revealed cell-specific mechanisms for maintaining mitochondrial NAD+ concentrations.

Original languageEnglish (US)
Pages (from-to)1474-1477
Number of pages4
JournalScience
Volume352
Issue number6292
DOIs
StatePublished - Jun 17 2016

ASJC Scopus subject areas

  • General

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    Cambronne, X. A., Stewart, M. L., Kim, D., Jones-Brunette, A. M., Morgan, R. K., Farrens, D. L., Cohen, M. S., & Goodman, R. H. (2016). Biosensor reveals multiple sources for mitochondrial NAD+. Science, 352(6292), 1474-1477. https://doi.org/10.1126/science.aad5168