Biosensor reveals multiple sources for mitochondrial NAD+

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

Research output: Contribution to journalArticle

92 Citations (Scopus)

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

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Biosensing Techniques
NAD
Sirtuins
Mitochondria
Enzymes
Adenosine Diphosphate Ribose
Poly Adenosine Diphosphate Ribose
Cytosol
Cytoplasm

ASJC Scopus subject areas

  • General

Cite this

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

Biosensor reveals multiple sources for mitochondrial NAD+. / Cambronne, Xiaolu; Stewart, Melissa L.; Kim, Dongho; Jones-Brunette, Amber M.; Morgan, Rory K.; Farrens, David; Cohen, Michael; Goodman, Richard.

In: Science, Vol. 352, No. 6292, 17.06.2016, p. 1474-1477.

Research output: Contribution to journalArticle

Cambronne, X, Stewart, ML, Kim, D, Jones-Brunette, AM, Morgan, RK, Farrens, D, Cohen, M & Goodman, R 2016, 'Biosensor reveals multiple sources for mitochondrial NAD+', Science, vol. 352, no. 6292, pp. 1474-1477. https://doi.org/10.1126/science.aad5168
Cambronne X, Stewart ML, Kim D, Jones-Brunette AM, Morgan RK, Farrens D et al. Biosensor reveals multiple sources for mitochondrial NAD+. Science. 2016 Jun 17;352(6292):1474-1477. https://doi.org/10.1126/science.aad5168
Cambronne, Xiaolu ; Stewart, Melissa L. ; Kim, Dongho ; Jones-Brunette, Amber M. ; Morgan, Rory K. ; Farrens, David ; Cohen, Michael ; Goodman, Richard. / Biosensor reveals multiple sources for mitochondrial NAD+. In: Science. 2016 ; Vol. 352, No. 6292. pp. 1474-1477.
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