The DOI matches its Crossref record; 130 of the 130 references it cites were found in a registry or an index.
Location, Location, Location: Compartmentalization of NAD+ Synthesis and Functions in Mammalian Cells
Open accessAbstract
The numerous biological roles of NAD+ are organized and coordinated via its compartmentalization within cells. The spatial and temporal partitioning of this intermediary metabolite is intrinsic to understanding the impact of NAD+ on cellular signaling and metabolism. We review evidence supporting the compartmentalization of steady-state NAD+ levels in cells, as well as how the modulation of NAD+ synthesis dynamically regulates signaling by controlling subcellular NAD+ concentrations. We further discuss potential benefits to the cell of compartmentalizing NAD+, and methods for measuring subcellular NAD+ levels.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“NAD+ is highly compartmentalized in the cytoplasm, mitochondria and nucleus, which represent its main subcellular pools (Supplementary Box 1).”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [2]
In the citing paper
“These pools are regulated independently of each other, and consistent with this, the enzymes involved in the biosynthesis or degradation of NAD+ are highly compartmentalized as well2–4.”
From NAD+ metabolism and its roles in cellular processes during ageing (2021) · cites this paper as [2]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Ultrasensitive fluorescent proteins for imaging neuronal activity
Chen, T.-W., Wardill, T. J., Sun, Y., Pulver, S. R., Renninger, S. L., Baohan, A., Schreiter, E. R., Kerr, R. A., Orger, M. B., Jayaraman, V., et al. (2013) · Nature · doi:10.1038/nature12354 · Cited by 6,474
Understanding the Intersections between Metabolism and Cancer Biology
Heiden, M. G. V., & DeBerardinis, R. J. (2017) · Cell · doi:10.1016/j.cell.2016.12.039 · Cited by 2,369
Sirtuins as regulators of metabolism and healthspan
Houtkooper, R. H., Pirinen, E., & Auwerx, J. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3293 · Cited by 2,008
Williamson, D., Lund, P., & Krebs, H. (1967) · Biochemical Journal · doi:10.1042/bj1030514 · Cited by 1,871
Gomes, A. P., Price, N. L., Ling, A. J. Y., Moslehi, J. J., Montgomery, M. K., Rajman, L., White, J. P., Teodoro, J. S., Wrann, C. D., Hubbard, B. P., et al. (2013) · Cell · doi:10.1016/j.cell.2013.11.037 · Cited by 1,482
NAD+ and sirtuins in aging and disease
Imai, S.-I., & Guarente, L. (2014) · Trends in Cell Biology · doi:10.1016/j.tcb.2014.04.002 · Cited by 1,481
New insights into the molecular and cellular functions of poly(ADP-ribose) and PARPs
Gibson, B. A., & Kraus, W. L. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3376 · Cited by 1,226
Self-citationCircadian Control of the NAD + Salvage Pathway by CLOCK-SIRT1
Nakahata, Y., Sahar, S., Astarita, G., Kaluzova, M., & Sassone-Corsi, P. (2009) · Science · doi:10.1126/science.1170803 · Cited by 1,198
Circadian Clock Feedback Cycle Through NAMPT-Mediated NAD + Biosynthesis
Ramsey, K. M., Yoshino, J., Brace, C. S., Abrassart, D., Kobayashi, Y., Marcheva, B., Hong, H.-K., Chong, J. L., Buhr, E. D., Lee, C., et al. (2009) · Science · doi:10.1126/science.1171641 · Cited by 1,126
NAD(H) and NADP(H) Redox Couples and Cellular Energy Metabolism
Xiao, W., Wang, R., Handy, D. E., & Loscalzo, J. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7216 · Cited by 1,062
Flagged first, then by citations
Research works printed but not linked: 1
- Nikiforov, 2011, Pathways and subcellular compartmentation of NAD biosynthesis in human cells: from entry of extracellular precursors to mitochondrial NAD generation, J. Biol. Chem., 286, 21767, 10.1074/jbc.M110.213298 · DOI · Paper page
Cited by
Sorted by citations
Items 101–137 of 137
Mechanisms of NAD+ Homeostasis in Aging and Disease
McReynolds, M. R. (2026) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-112525-013335 · Cited by 2
Coluccia, M., Secci, D., & Guglielmi, P. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-823974-2.00024-3 · Cited by 2
Evaluation of the Role of PnuC Gene in Enhancing Nicotinamide Mononucleotide Synthesis
Vo, G. T. T., Nguyen, K. K. H., & Kim, B. S. (2025) · Biotechnology and Applied Biochemistry · doi:10.1002/bab.2713 · Cited by 2
Zinc toxicity induces intestinal cell death via inhibiting NAD+ synthesis in mice and IPEC-J2 cells
Chen, L., Huang, F., Zhu, L., Tian, X., Zhou, M., & Feng, J. (2025) · Animal Nutriomics · doi:10.1017/anr.2025.10008 · Cited by 2
Stokes, M. S., Kim, Y. J., Kim, Y., Koul, S., Chiu, S.-P., Dasovich, M., Zuniga, J., Nandu, T. S., Huang, D. Y., Mathews, T. P., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.04.07.647692 · Cited by 2
Self-citationBuilding Localized NADP(H) Recycling Circuits to Advance Enzyme Cascadetronics
Herold, R. A., Schofield, C. J., & Armstrong, F. A. (2025) · Angewandte Chemie · doi:10.1002/ange.202414176 · Cited by 1
Yi, Z., Juvvadi, N., Zhai, R. G., Moraes, C. T., & Pinto, M. (2026) · Mitochondrial Communications · doi:10.1016/j.mitoco.2026.01.001 · Cited by 2
Mitochondrial NADP(H) integrates redox and metabolism
Zhang, R., & Zhang, K. (2026) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2025.12.003 · Cited by 1
Metabolic Flux Adaptations During GLP-1 Receptor Agonist Therapy: Redox Implications
Lee, J., You, J. H., Park, H. J., Roh, J.-L., & Paek, S. H. (2026) · Current Obesity Reports · doi:10.1007/s13679-026-00709-4 · Cited by 1
Disruption of myocardial NAD⁺ balance in heart failure: Mechanisms and therapeutic opportunities
Sundaresan, S., & Hottiger, M. O. (2026) · Disease and Therapeutics · doi:10.1016/j.dist.2026.100008 · Cited by 1
Targeting NAD Homeostasis: Compartmentalization, Quantification, and Modulation
Nobile, M., Fontanini, V., Serrao, S., Burtscher, J., Re, F., & Paglia, G. (2026) · Metabolites · doi:10.3390/metabo16050338 · Cited by 1
“One particularly underexplored aspect concerns how NAD-targeting interventions affect intracellular NAD compartmentalization and the activity of NAD-dependent metabolic pathways within specific organelles [27].”
InfluentialMedoro, A., Davinelli, S., Mazzotta, C. G., Agnifili, L., & Scapagnini, G. (2026) · Pharmaceuticals · doi:10.3390/ph19081268 · Cited by 1
“The salvage pathway recycles NAM released by NAD + - consuming reactions and is the quantitatively dominant route in most extrahepatic tissues, including the retina [19,22].”
SLC25A51 impacts drug sensitivity in AML cells by sustaining mitochondrial oxidative fluxPreprint
Lu, M., Busquets, J., Impedovo, V., Chang, Y.-T., Matsui, W. H., Tiziani, S., & Cambronne, X. A. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.11.15.516643 · Cited by 1
Self-citationNMNAT1 Binding at Promoters and Enhancers Couples NAD + Synthesis to RNA Polymerase II EngagementPreprint
Cedeno, Y. C., Taylor, S. J., Gamble, M. J., Steidl, U. G., & Coleman, R. A. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.04.30.651499 · Cited by 1
“NAD ⁺ is a central coenzyme with essential roles in redox metabolism, DNA repair, and gene regulation 14–20 .”
Damschroder, D., Perez, R. Z., Houtkooper, R. H., & Wessells, R. J. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.01.06.475267
A chemical solution for FRET(ful) pairs
Lyons, S. N., & Cambronne, X. A. (2023) · Nature Chemical Biology · doi:10.1038/s41589-023-01403-5
Self-citationLiu, J., Zhu, Y., Canic, T., Diaz-Perez, Z., Gultekin, S. H., & Zhai, R. G. (2025) · Neuro-Oncology Advances · doi:10.1093/noajnl/vdaf029
“38 As the adenylyltransferase catalyzes the last step of NAD + synthesis, NMNAT proteins are compartmentalized to support the local production of NAD + .”
Identification, Source, and Intracellular Distribution of Nicotinamide Coenzyme I
Shen, J., Li, S., Liu, N., Huang, Q., Rui, Y., & Wang, Y. (2025) · Springer eBooks · doi:10.1007/978-981-97-9877-3_3
Olatomide, O. D., Musa, S. A., Bauchi, Z. M., Sambo, S. J., Agbon, A. N., Omoniyi, A. A., & Abolaji, A. O. (2025) · Research Square · doi:10.21203/rs.3.rs-7474241/v1
Rahman, M. S., Hasib, R. A., Rahman, M. R., Biswas, P. K., Reza, A., Khatun, M., & Jamal, M. A. H. M. (2025) · Tumor Biology · doi:10.1177/14230380251410470
Lu, M., Chan, H., Deme, S., Oliphint, P. A., Kim, J., Allard, P., & Cambronne, X. A. (2025) · Stem Cells · doi:10.1093/stmcls/sxaf081 · Cited by 1
Self-citationNAD+ Homeostasis and Mitochondrial Modifiability: Resilience in Alzheimer’s Disease
Stefano, G. B. (2026) · Frontiers in Bioscience-Landmark · doi:10.31083/fbl49714
Nitta, Y., Yamamoto, M., Yaku, K., Uchida, H., Hayashi, A., & Nakagawa, T. (2026) · Journal of Nutritional Science and Vitaminology · doi:10.3177/jnsv.72.131
“SelO”ective NAD+ hydrolysis regulates mitochondrial NAD+ and homeostasis
Zhang, Q. F., Tan, T. C. M., & Sorrentino, V. (2026) · Cell chemical biology · doi:10.1016/j.chembiol.2026.04.012
Abe, K., Nozawa, H., Sonoda, H., Taira, T., Sasaki, K., Murono, K., Emoto, S., Yokoyama, Y., Nagai, Y., Harada, Y., et al. (2026) · Research Square · doi:10.21203/rs.3.rs-9417183/v1
Role of sirtuins in glucose and lipid metabolism
Swastik, V., & Kotnis, A. L. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-45380-9.00003-1
Ruedas, P., Gruß, H., Hempelmann, A., Vranic, M., Neuberth, S., Petrich, V., Gross, D., Pálfí, A., Pahl, A. M., & Hechler, T. (2026) · ACS Bio & Med Chem Au · doi:10.1021/acsbiomedchemau.6c00047
Tankyrase‐2 regulates adipocyte differentiation through AMPK / mTOR signaling
Rauch, B., Ujlaki, G., Póliska, S., Murahwa, N., Kovács, P., Pettkó‐Szandtner, A., Uray, K., & Bai, P. (2026) · FEBS Journal · doi:10.1111/febs.70676
Peripheral Neuropathy in Metabolic Stress
Fu, K., Yang, J. H., & Cao, Y. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27167301
“Three isoforms of NMNATs are expressed in mammalian cells, i.e., NMNAT1, NM-NAT2, and NMNAT3, with distinct subcellular localizations [25,26].”
Leng, Y., Bao, W., Ma, C., Bao, R., Bao, Y., Zhai, Z., Htar, T. T., & Wang, L. (2026) · Chemical & Biomedical Imaging · doi:10.1021/cbmi.6c00122 · Cited by 2
Grycan, M., Zyśk, R., Grycan, G., Jakiel, G., Dudek, A., & Gromadzka, G. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27177521
Zhu, J., Li, J., Qin, Y., Cui, Y., & Mou, L. (2026) · Nutrition Reviews · doi:10.1093/nutrit/nuag128
Lysine Acetylation as a Regulatory Mechanism in Cardiometabolic Disease: A Focus on Sirtuins
Trivedi, K., & Dolinsky, V. W. (2026) · Pharmaceuticals · doi:10.3390/ph19101557
“Within the cell, NAD + is compartmentalized in the nucleus, cytosol and mitochondria [140,142].”
BindingDB (2025) · UC San Diego · doi:10.7270/q25x2fk7
BindingDB Entry 50020539: The evolution of small molecule enzyme activators.
BindingDB (2024) · UC San Diego · doi:10.7270/q2b56q63
Elucidating the effect of spatial localization on metabolic systems
Almutairi, A., & Krishnan, J. (2026) · Journal of The Royal Society Interface · doi:10.1098/rsif.2025.1328
Metadata
- Authors
- Cambronne, X. A., & Kraus, W. L.
- Affiliations
- The University of Texas at Austin (US)
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Cambronne, Xiaolu A.
- Kraus, W. Lee
- Venue
- Trends in Biochemical Sciences
- Publisher
- Elsevier BV
- Published
- 2020-10
- Volume
- 45
- Issue
- 10
- Pages
- 858-873
- ISSN
- 0968-0004 (ISSN-L)
- PMC
- PMC7502477
- OpenAlex
- W3037844642
- Cited by
- 137
- References
- 130
- Citations by year
- 2026: 25 · 2025: 23 · 2024: 26 · 2023: 25 · 2022: 21 · 2021: 15 · 2020: 2
- FWCI
- 1.95
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Trends in Biochemical Sciences (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- NAD+, compartmentalization, NAD+ synthesis, cellular metabolism, signal transduction, subcellular compartmentalization
- MeSH terms
- Animals, Cell Compartmentation, NAD, Subcellular Fractions, Signal Transduction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review