ArticleNature genetics2018
Compartmentalized activities of the pyruvate dehydrogenase complex sustain lipogenesis in prostate cancer.
Article in Nature genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 112 papers.
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Who cites it
112 citing papers in PubMed, 193 citations in OpenAlex.
- Dynamic regulation of H3K9 modifications in cancer: pathogenesis and targeted therapies.Biomarker research · 2026Review
- Regulation of PDH via cysteine oxidation on DLAT.Nature communications · 2026Article
- PDHA1 Hyperactivation-Mediated Glucose Metabolism Reprogramming Fuels Neutrophil NETosis and Promotes Acute Lung Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Acetyl-CoA-dependent processes are preferentially supported by local metabolite synthesis.Science advances · 2026Article
- Histone modifications: mechanisms, metabolic regulation, and therapeutic targeting in cancer.Precision clinical medicine · 2026Review
- Mapping prostate cancer pathobiology: A review of genetically engineered mouse models (GEMMs).Gene · 2026Review
- Regulation of pyruvate dehydrogenase complex: Dancing to different drums in cancer.International journal of cancer · 2026Review
- PDHA1 enhances resistance to ferroptosis in anoikis-resistant prostate cancer by upregulating AIFM2.Cell death discovery · 2026Article
- Hallmarks of nuclear metabolism: implications for genome integrity, nuclear signaling, and therapeutic targeting.npj metabolic health and disease · 2026Review
- The Pyruvate Dehydrogenase Complex: A 90-Year-Old Enigma Shaping the Future of Structural Enzymology.Advances in experimental medicine and biology · 2026Review
- PDHA1 Hyperactivation Orchestrates Metabolic Reprogramming Promoting Endothelial Senescence.Research (Washington, D.C.) · 2026Article
- Mitochondrial convergence of ferroptosis and cuproptosis in castration-resistant prostate cancer: From metabolic vulnerabilities to therapeutic targeting.BBA advances · 2026Review
- Targeting p300 and CBP abolishes HOXB13-loss-induced lipogenesis and tumor metastasis.JCI insight · 2025Article
- TCA-cycle metabolites in the nucleus: drivers of chromatin and epigenetic control.BMC biology · 2025Review
- ACSL5 regulated acetyl-CoA to promote bladder cancer cellular senescence via 53BP1 acetylation.Oncogene · 2025Article
- A lncRNA-mediated metabolic rewiring of cell senescence.Cell reports · 2025Article
- Targeting Prostate Cancer Metabolism Through Transcriptional and Epigenetic Modulation: A Multi-Target Approach to Therapeutic Innovation.International journal of molecular sciences · 2025Review
- Cholangiocarcinoma PDHA1 succinylation suppresses macrophage antigen presentation via alpha-ketoglutaric acid accumulation.Nature communications · 2025Article
- Mitochondrial KMT9 methylates DLAT to control pyruvate dehydrogenase activity and prostate cancer growth.Nature communications · 2025Article
- DLAT is involved in ovarian cancer progression by modulating lipid metabolism through the JAK2/STAT5A/SREBP1 signaling pathway.Cancer cell international · 2025Article
52 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
30 authors at 11 institutions in 6 countries.
Funding
Abstract
The mechanisms by which mitochondrial metabolism supports cancer anabolism remain unclear. Here, we found that genetic and pharmacological inactivation of pyruvate dehydrogenase A1 (PDHA1), a subunit of the pyruvate dehydrogenase complex (PDC), inhibits prostate cancer development in mouse and human xenograft tumor models by affecting lipid biosynthesis. Mechanistically, we show that in prostate cancer, PDC localizes in both the mitochondria and the nucleus. Whereas nuclear PDC controls the expression of sterol regulatory element-binding transcription factor (SREBF)-target genes by mediating histone acetylation, mitochondrial PDC provides cytosolic citrate for lipid synthesis in a coordinated manner, thereby sustaining anabolism. Additionally, we found that PDHA1 and the PDC activator pyruvate dehydrogenase phosphatase 1 (PDP1) are frequently amplified and overexpressed at both the gene and protein levels in prostate tumors. Together, these findings demonstrate that both mitochondrial and nuclear PDC sustain prostate tumorigenesis by controlling lipid biosynthesis, thus suggesting this complex as a potential target for cancer therapy.
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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.