ArticleMolecular cell2023
Uncoupled glycerol-3-phosphate shuttle in kidney cancer reveals that cytosolic GPD is essential to support lipid synthesis.
Article in Molecular cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 39 citations in OpenAlex.
- Reply to Lemieux et al.: Integration does not preclude essentiality of mitochondrial glycerol-3-phosphate dehydrogenase.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Conserved principles of central carbon partitioning in Hippo-Yorkie-drivenbioRxiv : the preprint server for biology · 2026Article
- GPD1L supports glycerol-3-phosphate and triacylglycerol synthesis and promotes tumor progression in HCC.Hepatology (Baltimore, Md.) · 2026Article
- Aspartate availability drives differential engagement of the malate-aspartate shuttle.Molecular cell · 2026Article
- Construction and validation of a palmitoylation-related prognostic model for lung adenocarcinoma based on integrated bioinformatics and machine learning.Translational cancer research · 2026Article
- Integrated multi-omics analysis reveals GPD1L-mediated dysregulation of glycerophospholipid metabolism facilitates the progression of lung adenocarcinoma.Respiratory research · 2026Article
- A genetically encoded bifunctional enzyme mitigates redox imbalance and lipotoxicity.Nature metabolism · 2026Article
- Targeting glycerophospholipid biosynthesis overcomes chemoresistance driven by SLFN11 loss in Ewing sarcoma.Cell death & disease · 2026Article
- Epigenetically-controlled CEBPB regulates kidney cancer tumorigenesis via GPD1L-mediated ether lipid synthesis.Cell death & disease · 2026Article
- Site-specific HPV18 integration facilitates cervical carcinogenesis through metabolic reprogramming-induced dysfunction of the SpHK1/S1P/S1PR1 pathway.Cell death & disease · 2026Article
- CTRP9 ameliorates heart failure with preserved ejection fraction by regulating lipid metabolism.Journal of translational medicine · 2026Article
- Glutamine metabolism and its roles in tumor radiotherapy by regulating DNA damage repair.Frontiers in cell and developmental biology · 2026Review
- Catabolic rewiring in cancer impacts dietary interventions.Communications biology · 2025Review
- The role of GPD2 and glycolysis-related genes in cholangiocarcinoma: insights into prognostic biomarkers and tumor-immune interactions.Cancer cell international · 2025Article
- Glutamine antagonism suppresses tumor growth in adrenocortical carcinoma through inhibition of de novo nucleotide biosynthesis.bioRxiv : the preprint server for biology · 2025Article
- Identification of Key Biomarkers Related to Lipid Metabolism in Acute Pancreatitis and Their Regulatory Mechanisms Based on Bioinformatics and Machine Learning.Biomedicines · 2025Article
- The source of dietary fat influences anti-tumour immunity in obese mice.Nature metabolism · 2025Article
- D-lactate and glycerol as potential biomarkers of sorafenib activity in hepatocellular carcinoma.Signal transduction and targeted therapy · 2025Article
- Catalytically distinct metabolic enzyme isocitrate dehydrogenase 1 mutants tune phenotype severity in tumor models.The Journal of biological chemistry · 2025Article
- Upregulated FSP1 by GPD1/1L mediated lipid droplet accumulation enhances ferroptosis resistance and peritoneal metastasis in gastric cancer.Cell communication and signaling : CCS · 2025Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
The glycerol-3-phosphate shuttle (G3PS) is a major NADH shuttle that regenerates reducing equivalents in the cytosol and produces energy in the mitochondria. Here, we demonstrate that G3PS is uncoupled in kidney cancer cells where the cytosolic reaction is ∼4.5 times faster than the mitochondrial reaction. The high flux through cytosolic glycerol-3-phosphate dehydrogenase (GPD) is required to maintain redox balance and support lipid synthesis. Interestingly, inhibition of G3PS by knocking down mitochondrial GPD (GPD2) has no effect on mitochondrial respiration. Instead, loss of GPD2 upregulates cytosolic GPD on a transcriptional level and promotes cancer cell proliferation by increasing glycerol-3-phosphate supply. The proliferative advantage of GPD2 knockdown tumor can be abolished by pharmacologic inhibition of lipid synthesis. Taken together, our results suggest that G3PS is not required to run as an intact NADH shuttle but is instead truncated to support complex lipid synthesis in kidney cancer.
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