ArticleMolecular metabolism2022
Multiple metabolic pathways fuel the truncated tricarboxylic acid cycle of the prostate to sustain constant citrate production and secretion.
Article in Molecular metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Unravelling deregulated metabolites in seminal plasma of infertile men: a systematic review and bioinformatic analysis.Journal of molecular medicine (Berlin, Germany) · 2026Pooled it
- SARIFA and Lipid Metabolic Reprogramming in Prostate Cancer: Fundamental Mechanisms, Tumor Microenvironment, and Novel Biomarker Prospects.Life (Basel, Switzerland) · 2026Review
- Copper-EGCG nanoreactor orchestrates dual-metabolic assault and self-amplified cuproptosis for immunogenic prostate cancer therapy.Journal of nanobiotechnology · 2026Article
- ASCC3 promotes chemosensitivity in colorectal cancer cells.Scientific reports · 2026Article
- The mTOR signaling pathway regulates key steps of mammary gland organoid genesis in a temporal manner.Scientific reports · 2026Article
- Cuproptosis and prostate cancer: from molecular mechanisms and microenvironment remodeling to precision therapy.Frontiers in oncology · 2026Review
- Metagenomics and metabolomics analyses of the mechanism of non-expression of natural mating behavior in captive male Malayan pangolins (Frontiers in microbiology · 2026Article
- PRSS55 regulates BCAA metabolism and interacts with BCKDK and BCKDHA in mouse testes and sperm.Cell & bioscience · 2025Article
- Perimenopausal state oestradiol to progesterone imbalance drives Alzheimer's risk via ERRα dysregulation and energy dyshomeostasis.Nature communications · 2025Article
- Reprogrammed Lipid Metabolism-Associated Therapeutic Vulnerabilities in Prostate Cancer.International journal of molecular sciences · 2025Review
- Crosstalk between mitochondrial dysfunction and benign prostatic hyperplasia: unraveling the intrinsic mechanisms.The Canadian journal of urology · 2025Review
- Variations in Human Milk Metabolites After Gestational Diabetes: Associations with Infant Growth.Nutrients · 2025Article
- Slowly digestible starch impairs growth performance of broiler chickens offered low-protein diet supplemental higher amino acid densities by inhibiting the utilization of intestinal amino acid.Journal of animal science and biotechnology · 2025Article
- Metabolic adaptations in prostate cancer.British journal of cancer · 2024Review
- Rediscovering citrate as a biomarker for prostate cancer.Nature reviews. Urology · 2024Article
- Single-cell sequencing revealed metabolic reprogramming and its transcription factor regulatory network in prostate cancer.Translational oncology · 2024Article
- HSDL2 links nutritional cues to bile acid and cholesterol homeostasis.Science advances · 2024Article
- Article
- Concentric Hybrid Nanoelectrospray Ionization-Atmospheric Pressure Chemical Ionization Source for High-Coverage Mass Spectrometry Analysis of Single-Cell Metabolomics.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Organoids transplantation attenuates intestinal ischemia/reperfusion injury in mice through L-Malic acid-mediated M2 macrophage polarization.Nature communications · 2023Article
Corrections and comments
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Authors and funding
17 authors at 1 institution in 1 country.
Funding
Abstract
objectiveThe prostate is metabolically unique: it produces high levels of citrate for secretion via a truncated tricarboxylic acid (TCA) cycle to maintain male fertility. In prostate cancer (PCa), this phenotype is reprogrammed, making it an interesting therapeutic target. However, how the truncated prostate TCA cycle works is still not completely understood.
methodsWe optimized targeted metabolomics in mouse and human organoid models in ex vivo primary culture. We then used stable isotope tracer analyses to identify the pathways that fuel citrate synthesis.
resultsFirst, mouse and human organoids were shown to recapitulate the unique citrate-secretory program of the prostate, thus representing a novel model that reproduces this unusual metabolic profile. Using stable isotope tracer analysis, several key nutrients were shown to allow the completion of the prostate TCA cycle, revealing a much more complex metabolic profile than originally anticipated. Indeed, along with the known pathway of aspartate replenishing oxaloacetate, glutamine was shown to fuel citrate synthesis through both glutaminolysis and reductive carboxylation in a GLS1-dependent manner. In human organoids, aspartate entered the TCA cycle at the malate entry point, upstream of oxaloacetate. Our results demonstrate that the citrate-secretory phenotype of prostate organoids is supported by the known aspartate-oxaloacetate-citrate pathway, but also by at least three additional pathways: glutaminolysis, reductive carboxylation, and aspartate-malate conversion.
conclusionsOur results add a significant new dimension to the prostate citrate-secretory phenotype, with at least four distinct pathways being involved in citrate synthesis. Better understanding this distinctive citrate metabolic program will have applications in both male fertility as well as in the development of novel targeted anti-metabolic therapies for PCa.
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