ArticleCell metabolism2020
Serine Catabolism Feeds NADH when Respiration Is Impaired.
Article in Cell metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers.
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Who cites it
119 citing papers in PubMed, 201 citations in OpenAlex.
- Sulfur amino acid restriction and caloric restriction induce divergent redox metabolism-related adaptations in male F344 rats.Redox report : communications in free radical research · 2026Article
- Folate metabolism in tumor-associated macrophages drives immunosuppressive function to promote tumor growth.bioRxiv : the preprint server for biology · 2026Article
- Nicotinamide nucleotide transhydrogenase directly couples redox homeostasis to proline biosynthesis in human glioma.Molecular cell · 2026Article
- Polyunsaturated fatty acid sequestration protects against mitochondrial dysfunction-induced ferroptosis.EMBO reports · 2026Article
- Targeting serine metabolism boosts antimycobacterial immunity during Mycobacterium tuberculosis H37Rv infection.Molecules and cells · 2026Article
- Mitochondrial NADH-redox inflexibility constrains genomic and epigenetic stability in pluripotent stem cells.The EMBO journal · 2026Article
- RegB/A-dependent redox regulation links iron uptake to methanol metabolism inApplied and environmental microbiology · 2026Article
- Phenazine Methosulfate Rewires Mitochondrial Redox Circuits to Restore Membrane Potential and ATP Synthesis Under ETC Blockade in Glioblastoma Cells.Antioxidants (Basel, Switzerland) · 2026Article
- Normoxic HIFα-mediated metabolic rewiring in cancer as a novel therapeutic target of tumor heterogeneity.Cancer & metabolism · 2026Article
- MTHFD2: a promising metabolic checkpoint for diseases.Journal of translational medicine · 2026Review
- Serine Hydroxymethyltransferase (SHMT) in biology and disease: molecular mechanisms and therapeutic targeting.Journal of translational medicine · 2026Review
- Copper-rhein nanozymes induce bacterial activation-exhaustion death for the treatment of bacterial pneumonia and infected wounds.Journal of nanobiotechnology · 2026Article
- MTHFD2 modulates neural stem cell proliferation and apoptosis after intracerebral hemorrhage by regulating mitochondrial NADPH homeostasis.Journal of translational medicine · 2026Article
- Mitochondrial uncoupling inhibits serine catabolismCancer biology & medicine · 2026Article
- ΔNp63α drives serine synthesis to promote carboplatin resistance in NSCLC.Cell death & disease · 2026Article
- Mitochondrial formate dehydrogenase links mitochondrial and cytosolic one carbon metabolism via a one-carbon shunt.Plant physiology · 2026Review
- Despite inducing antioxidant regulation, superoxide dismutase deficiency makesFrontiers in microbiology · 2026Article
- An Alternative Metabolic Pathway of Glucose Oxidation Induced by Mitochondrial Complex I Inhibition: Serinogenesis and Folate Cycling.International journal of molecular sciences · 2025Article
- MTHFD2: A Retrospective and a Glance into the Future.International journal of molecular sciences · 2025Review
- Variation in metabolic pattern regulation under hypoxic conditions: a comparative study of rodents distributed at different altitudes.Frontiers in zoology · 2025Article
59 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 5 institutions in 4 countries.
Funding
Abstract
NADH provides electrons for aerobic ATP production. In cells deprived of oxygen or with impaired electron transport chain activity, NADH accumulation can be toxic. To minimize such toxicity, elevated NADH inhibits the classical NADH-producing pathways: glucose, glutamine, and fat oxidation. Here, through deuterium-tracing studies in cultured cells and mice, we show that folate-dependent serine catabolism also produces substantial NADH. Strikingly, when respiration is impaired, serine catabolism through methylene tetrahydrofolate dehydrogenase (MTHFD2) becomes a major NADH source. In cells whose respiration is slowed by hypoxia, metformin, or genetic lesions, mitochondrial serine catabolism inhibition partially normalizes NADH levels and facilitates cell growth. In mice with engineered mitochondrial complex I deficiency (NDUSF4-/-), serine's contribution to NADH is elevated, and progression of spasticity is modestly slowed by pharmacological blockade of serine degradation. Thus, when respiration is impaired, serine catabolism contributes to toxic NADH accumulation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.