ArticleNature cell biology2025
AMPK-regulated glycerol excretion maintains metabolic crosstalk between reductive and energetic stress.
Article in Nature cell biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Harnessing probiotic-metformin synergy: targeting the gut-microbiota metabolism axis to ameliorate polycystic ovary syndrome.Frontiers in nutrition · 2025Pooled it
- Olaparib Blocks Oxidative Stress-Dependent NLRP3 Inflammasome in Pediatric Acute Lung Injury by Metabolic Reprogramming via AMPK-Driven Autophagic Flux.The Kaohsiung journal of medical sciences · 2026Article
- Histone H4K5 lactylation-driven feedback loop modulates glycerol-linked immunosuppressive activity of tumor-associated T regulatory cells.Signal transduction and targeted therapy · 2026Article
- Metabolic circuitry of NADH buffering reveals a vulnerability in redox-adaptive cancer cells.Innovation (Cambridge (Mass.)) · 2026Article
- The Reductive Stress Nexus: Integrated Pathways of Metabolic Dysregulation, Senescence and Blood-Brain Barrier Failure in Neurodegenerative Disease and Brain Aging.Cell biochemistry and biophysics · 2026Review
- Chemical Bond-Orchestrated Energy Depletion to Augment Lung Cancer Chemo-Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Reductive Stress and Ferroptosis: Linking Insulin Signaling to Metabolic Dysfunction.Biomolecules · 2026Review
- Metabolic rewiring driven by phosphoglycolate phosphatase deletion inhibits ferroptosis.Science advances · 2026Article
- Article
- GPR109a-AMPK axis mediates the Attenuation of uric acid-induced M1 macrophage polarization by β-hydroxybutyrate from Lacticaseibacillus rhamnosus M2b.Scientific reports · 2026Article
- The AMPK/NRF2/FOXO Axis in CKD-Molecular and Clinical Perspectives.Antioxidants (Basel, Switzerland) · 2026Review
- Unveiling membrane transporter proteins-related genes for predicting the prognosis of hepatocellular carcinoma patients.Discover oncology · 2026Article
- A genetically encoded bifunctional enzyme mitigates redox imbalance and lipotoxicity.Nature metabolism · 2026Article
- Structure, Mutation, Functional Domain Roles and Medical Implications of Glycerol Kinase.The protein journal · 2026Review
- Reductive stress in cancer immunology and targeted therapy.Acta biochimica et biophysica Sinica · 2026Review
- Epigenetically-controlled CEBPB regulates kidney cancer tumorigenesis via GPD1L-mediated ether lipid synthesis.Cell death & disease · 2026Article
- Glycerol and Glycerol-3-Phosphate: Multifaceted Metabolites in Metabolism, Cancer, and Other Diseases.Endocrine reviews · 2026Review
- CTRP9 ameliorates heart failure with preserved ejection fraction by regulating lipid metabolism.Journal of translational medicine · 2026Article
- AMPK at the interface of nutrient sensing, metabolic flux and energy homeostasis.Nature metabolism · 2026Review
- Genome-wide analysis of theFrontiers in plant science · 2026Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Glucose metabolism has been studied extensively, but the role of glucose-derived excretory glycerol remains unclear. Here we show that hypoxia induces NADH accumulation to promote glycerol excretion and this pathway consumes NADH continuously, thus attenuating its accumulation and reductive stress. Aldolase B accounts for glycerol biosynthesis by forming a complex with glycerol 3-phosphate dehydrogenases GPD1 and GPD1L. Blocking GPD1, GPD1L or glycerol 3-phosphate phosphatase exacerbates reductive stress and suppresses cell proliferation under hypoxia and tumour growth in vivo. Overexpression of these enzymes increases glycerol excretion but still reduces cell viability under hypoxia and tumour proliferation due to energy stress. AMPK inactivates aldolase B to mitigate glycerol synthesis that dissipates ATP, alleviating NADH accumulation-induced energy crisis. Therefore, glycerol biosynthesis/excretion regulates the trade-off between reductive stress and energy stress. Moreover, this mode of regulation seems to be prevalent in reductive stress-driven transformations, enhancing our understanding of the metabolic complexity and guiding tumour treatment.
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39747579What OpenQuestion holds
Registered trials
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.