ArticleThe Journal of biological chemistry2015
Subcellular Distribution of NAD+ between Cytosol and Mitochondria Determines the Metabolic Profile of Human Cells.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 74 citations in OpenAlex.
- Mitochondrial CISD1 Modulates Microglial Metabolic Reprogramming to Drive Stress Susceptibility in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Precision Nanodelivery Enables Spatiotemporal Control of NAD⁺ Metabolism in Ageing and Disease.International journal of nanomedicine · 2026Review
- A sensory and motor neuropathy caused by a genetic variant ofScience advances · 2025Article
- Emerging interactions between mitochondria and NADTrends in endocrinology and metabolism: TEM · 2025Review
- Subcellular NADNature metabolism · 2024Article
- Pyroptosis of oral keratinocyte contributes to energy metabolic reprogramming of T cells in oral lichen planus via OPA1-mediated mitochondrial fusion.Cell death discovery · 2024Article
- Cytosolic RNA binding of the mitochondrial TCA cycle enzyme malate dehydrogenase.RNA (New York, N.Y.) · 2024Article
- Accounting for NAD Concentrations in Genome-Scale Metabolic Models Captures Important Metabolic Alterations in NAD-Depleted Systems.Biomolecules · 2024Article
- Visualizing subcellular changes in the NAD(H) pool size versus redox state using fluorescence lifetime imaging microscopy of NADH.Communications biology · 2024Article
- SLC25A51 decouples the mitochondrial NADCell metabolism · 2024Article
- Layered mechanisms regulating the human mitochondrial NAD+ transporter SLC25A51.Biochemical Society transactions · 2023Review
- Tiliroside suppresses triple-negative breast cancer as a multifunctional CAXII inhibitor.Cancer cell international · 2022Article
- Mitochondrial transport and metabolism of the vitamin B-derived cofactors thiamine pyrophosphate, coenzyme A, FAD and NADIUBMB life · 2022Review
- Overexpression of NMNAT3 improves mitochondrial function and enhances antioxidative stress capacity of bone marrow mesenchymal stem cells via the NAD+-Sirt3 pathway.Bioscience reports · 2022Article
- Welcome to the Family: Identification of the NADBiomolecules · 2021Review
- Maestro of the SereNADe: SLC25A51 Orchestrates Mitochondrial NADTrends in biochemical sciences · 2021Article
- Article
- Impaired Nicotinamide Adenine Dinucleotide Biosynthesis in the Kidney of Chronic Kidney Disease.Frontiers in physiology · 2021Article
- NADFrontiers in molecular biosciences · 2021Review
- Response to Oxidative Burst-Induced Hypoxia Is Associated With Macrophage Inflammatory Profiles as Revealed by Cellular Genome-Wide Association.Frontiers in immunology · 2021Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mitochondrial NAD pool is particularly important for the maintenance of vital cellular functions. Although at least in some fungi and plants, mitochondrial NAD is imported from the cytosol by carrier proteins, in mammals, the mechanism of how this organellar pool is generated has remained obscure. A transporter mediating NAD import into mammalian mitochondria has not been identified. In contrast, human recombinant NMNAT3 localizes to the mitochondrial matrix and is able to catalyze NAD(+) biosynthesis in vitro. However, whether the endogenous NMNAT3 protein is functionally effective at generating NAD(+) in mitochondria of intact human cells still remains to be demonstrated. To modulate mitochondrial NAD(+) content, we have expressed plant and yeast mitochondrial NAD(+) carriers in human cells and observed a profound increase in mitochondrial NAD(+). None of the closest human homologs of these carriers had any detectable effect on mitochondrial NAD(+) content. Surprisingly, constitutive redistribution of NAD(+) from the cytosol to the mitochondria by stable expression of the Arabidopsis thaliana mitochondrial NAD(+) transporter NDT2 in HEK293 cells resulted in dramatic growth retardation and a metabolic shift from oxidative phosphorylation to glycolysis, despite the elevated mitochondrial NAD(+) levels. These results suggest that a mitochondrial NAD(+) transporter, similar to the known one from A. thaliana, is likely absent and could even be harmful in human cells. We provide further support for the alternative possibility, namely intramitochondrial NAD(+) synthesis, by demonstrating the presence of endogenous NMNAT3 in the mitochondria of human cells.
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