ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Glycolysis-Derived Lactate Induces ACSL4 Expression and Lactylation to Activate Ferroptosis during Intervertebral Disc Degeneration.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed.
- Ferroptosis in cancer: molecular mechanisms, biological roles, and therapeutic significance.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Ammonia Accumulation Drives Intervertebral Disc Degeneration by Triggering Ammonia-Induced Cell Death Through Lysosome-Mitochondria Crosstalk.Cell proliferation · 2026Article
- Causal Effects of Plasma Metabolites on Intervertebral Disc Degeneration and Low Back Pain: A Mendelian Randomization Study.Metabolites · 2026Article
- SERPINE1/PAI-1 in Skeletal Degeneration: A Proposed Context-Dependent Framework for Bone Remodeling Regulation.Calcified tissue international · 2026Review
- TRIM25 facilitates mitochondrial dysfunction and extracellular matrix degradation by enhancing USP7-driven ENO1 deubiquitination during intervertebral disc degeneration.Clinical and translational medicine · 2026Article
- Histone Post-Translational Modifications Regulating Ferroptosis: The Molecular Mechanisms and Disease Associations.Cell biochemistry and function · 2026Review
- Lysosomal Dysfunction Is Associated With Intervertebral Disc Degeneration: Multiomics and Machine Learning Identify Molecular Subtypes and Hub Genes.The journal of gene medicine · 2026Article
- ACSL4-Dependent Lysosomal Lipid Peroxidation Links WTAP-Mediated mAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A Decoy-Receptor-Armed Biomimetic Nanotherapeutic With Inherent Tropism for Conserved Pathogenic Macrophages for Treating Osteoarthritis and Intervertebral Disc Degeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- [Research on ferroptosis induced by RSL3, Erastin, and TBHP in rat intervertebral disc annulus fibrosus cells].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2026Article
- MANF safeguards mitochondria-associated endoplasmic reticulum membrane integrity in nucleus pulposus-derived mesenchymal stem cells to maintain homeostasis of the intervertebral disc.Cell biology and toxicology · 2026Article
- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications.Signal transduction and targeted therapy · 2026Review
- Epigenetic research methods and animal models for intervertebral disc degeneration (Review).Molecular medicine reports · 2026Review
- Biomaterial-based strategies targeting ferroptosis for alleviating intervertebral disc degeneration: Advances and perspectives.Journal of orthopaedic translation · 2026Review
- Discovery of lactylation-associated candidate hub genes and potential curcumin targets in intervertebral disc degeneration.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- STAT3/POSTN/GSTP1/JNK Axis Orchestrates Ferroptosis in Nucleus Pulposus Cells: A Potential Therapeutic Target for Intervertebral Disc Degeneration.Neurospine · 2026Article
- The emerging role of lactate in skeletal homeostasis and disorders: Integrated mechanisms and translational opportunities.Journal of orthopaedic translation · 2026Review
- SETD1A Regulates Glycolysis and Senescence of Nucleus Pulposus Cells via H3K4me3-HELZ2/PPARα-HIF1α Axis to Drive Intervertebral Disc Degeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Inhibition of aerobic glycolysis suppresses ferroptosis via activation of the AMPK-FoxO3a pathway in epileptic rats.Molecular biology reports · 2026Article
- Lactylation-regulated ferroptosis: mechanisms, disease associations, and therapeutic strategies.Archives of pharmacal research · 2026Review
11 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors.
Funding
Abstract
The abnormal activation of the inflammatory microenvironment is frequently accompanied by metabolic changes that affect the development of various diseases. However, the relationship between metabolic reprogramming and intervertebral disc degeneration (IVDD) remains unclear. This study aims to reveal the metabolic changes in nucleus pulposus (NPCs) during IVDD and investigate the mechanism of glycolysis-derived lactate on NPCs. Single-cell RNA sequencing reveals that during IVDD, NPCs are characterized by excessively elevated glycolysis, and the resultant lactate causes the dysfunction of NPCs via ferroptosis activation. Mechanistically, lactate results in the transcription of Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4) via promoting Histon H3K18 lactylation. Interestingly, lactate can also increase the lactylation of ACSL4 at K412 site. In addition, lactate-induced decreased expression of Sirtuin-3 (SIRT3), and further cause the elevation of ACSL4 lactylation. Finally, animal experiments demonstrate that inhibiting glycolysis through gene silencing with adenoviral-associated viruses 9 (AAV9)-si-Ldha or chemical treatment using 2-deoxy-D-glucose can suppress lactate production and lactylation, thereby ameliorating ferroptosis and NPC dysfunction. The findings of this study indicate that lactate plays a crucial role in IVDD by activating ferroptosis and that interventions aimed at lactate production can offer a potential therapeutical option for patients with IVDD.
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