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Allosteric regulation of pyruvate kinase enables efficient and robust gluconeogenesis by preventing metabolic conflicts and carbon overflow.
mSystems
January 2025
Department of Bacteriology, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Gluconeogenesis, the reciprocal pathway of glycolysis, is an energy-consuming process that generates glycolytic intermediates from non-carbohydrate sources. In this study, we demonstrate that robust and efficient gluconeogenesis in bacteria relies on the allosteric inactivation of pyruvate kinase, the enzyme responsible for the irreversible final step of glycolysis. Using the model bacterium as an example, we discovered that pyruvate kinase activity is inhibited during gluconeogenesis via its extra C-terminal domain (ECTD), which is essential for autoinhibition and metabolic regulation.
View Article and Find Full Text PDFBET inhibition induces GDH1-dependent glutamine metabolic remodeling and vulnerability in liver cancer.
Life Metab
August 2024
Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai 200438, China.
Bromodomain and extra-terminal domain (BET) proteins, which function partly through MYC proto-oncogene (MYC), are critical epigenetic readers and emerging therapeutic targets in cancer. Whether and how BET inhibition simultaneously induces metabolic remodeling in cancer cells remains unclear. Here we find that even transient BET inhibition by JQ-1 and other pan-BET inhibitors (pan-BETis) blunts liver cancer cell proliferation and tumor growth.
View Article and Find Full Text PDFBrucea javanica oil inhibited the proliferation, migration, and invasion of oral squamous carcinoma by regulated the MTFR2 pathway.
Front Oncol
January 2025
Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, Jiangxi, China.
Introduction: Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors in oral and maxillofacial region. The development of new chemotherapy agents and new drug combinations may improve patient survival and quality of life, but both surgery and radiotherapy have significant functional side effects and drug resistance, ultimately resulting in a 5-year survival rate of no more than 60% for OSCC patients. Studies have shown that Brucea javanica oil (BJO) extracts have anti-cancer effects against a variety of cancers, but little research has been reported on OSCC.
View Article and Find Full Text PDFASIC1a mediated nucleus pulposus cells pyroptosis and glycolytic crosstalk as a molecular basis for intervertebral disc degeneration.
Inflamm Res
January 2025
Department of Orthopedics and Traumatology, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan Province, China.
Background: One of the etiologic components of degenerative spinal illnesses is intervertebral disc degeneration (IVDD), and the accompanying lower back pain is progressively turning into a significant public health problem. Important pathologic characteristics of IVDD include inflammation and acidic microenvironment, albeit it is unclear how these factors contribute to the disease.
Purpose: To clarify the functions of inflammation and the acidic environment in IVDD, identify the critical connections facilitating glycolytic crosstalk and nucleus pulposus cells (NPCs) pyroptosis, and offer novel approaches to IVDD prevention and therapy.
Dense stroma activates the TGF-β1/FBW7 axis to induce metabolic subtype switching in pancreatic cancer.
Int J Surg
January 2025
Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal diseases. Although several chemotherapy regimens have been developed over the past decades, few targeted therapies have shown a significant improvement in overall survival, partly due to the identification of PDAC as a single disease.
Methods: Combining metabolomic analysis and immunohistochemistry staining with Oil Red O staining, analysis for the oxygen consumption rate and extracellular acidification rate, we stratified pancreatic cancer cells into two subtypes.
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