ArticleNature metabolism2024
Glycolytic enzyme PFKL governs lipolysis by promoting lipid droplet-mitochondria tethering to enhance β-oxidation and tumor cell proliferation.
Article in Nature metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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95 citing papers in PubMed.
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- Post-translational modifications in metabolic reprogramming: implications for metabolic therapy and immunotherapy in cancer.Signal transduction and targeted therapy · 2026Review
- A covalent PFKL activator suppresses tumor growth.Nature chemical biology · 2026Article
- Fat on Fire: Disrupted Microglial Lipid Metabolism as a Driver of Anesthetic Neurotoxicity.Neuroscience bulletin · 2026Review
- Loss of Rab8a-Dependent Tethering of Lipid Droplets to Mitochondria Contributes to Hypoxia-Reoxygenation Injury.MedComm · 2026Article
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- Nitrate-Sialin2 axis couples ER-mitochondrial calcium signaling with fatty acid metabolism to drive white adipose browning.Nature communications · 2026Article
- Lipid droplets-mediated delivery of curcumin for targeted mitochondrial photodynamic therapy.International journal of pharmaceutics: X · 2026Article
- Pyruvate carboxylase promotes SREBP1a-mediated lipid synthesis in epithelial ovarian cancer.Communications biology · 2026Article
- Cycloastragenol Protects Against Cisplatin-Induced Cochlear Hair Cell Apoptosis via the PI3K/Akt/mTOR Pathway.Cellular and molecular neurobiology · 2026Article
35 more citing papers are in PubMed but not listed here.
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Abstract
Lipid droplet tethering with mitochondria for fatty acid oxidation is critical for tumor cells to counteract energy stress. However, the underlying mechanism remains unclear. Here, we demonstrate that glucose deprivation induces phosphorylation of the glycolytic enzyme phosphofructokinase, liver type (PFKL), reducing its activity and favoring its interaction with perilipin 2 (PLIN2). On lipid droplets, PFKL acts as a protein kinase and phosphorylates PLIN2 to promote the binding of PLIN2 to carnitine palmitoyltransferase 1A (CPT1A). This results in the tethering of lipid droplets and mitochondria and the recruitment of adipose triglyceride lipase to the lipid droplet-mitochondria tethering regions to engage lipid mobilization. Interfering with this cascade inhibits tumor cell proliferation, promotes apoptosis and blunts liver tumor growth in male mice. These results reveal that energy stress confers a moonlight function to PFKL as a protein kinase to tether lipid droplets with mitochondria and highlight the crucial role of PFKL in the integrated regulation of glycolysis, lipid metabolism and mitochondrial oxidation.
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