A method was devised to search for yeast mutants impaired in peroxisome functioning, indicating cross-talk between metabolic pathways. Two mutants were isolated; they are impaired in oleate utilisation and carry mutations in the KGD1 and LIP5 genes encoding the E1 component of the mitochondrial alpha-ketoglutarate dehydrogenase complex and lipoic acid synthase, respectively. The results presented indicate that the Kgd1 and Lip5 proteins are important for the expression of genes encoding peroxisomal matrix proteins, although they are not necessary for the biogenesis of this cellular compartment.
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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 PDFLife Metab
April 2024
State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
Isocitrate dehydrogenase (IDH) mutations frequently occur in lower-grade gliomas and secondary glioblastomas. Mutant IDHs exhibit a gain-of-function activity, leading to the production of D-2-hydroxyglutarate (D-2HG) by reducing α-ketoglutarate (α-KG), a central player in metabolism and epigenetic modifications. However, the role of α-KG homeostasis in IDH-mutated gliomagenesis remains elusive.
View Article and Find Full Text PDFInt Immunopharmacol
January 2025
Department of Immunology, Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, China. Electronic address:
Objective: Aberrant 6-phosphofructo-2kinase/fructose-2,6-bisphoshatase 3 (PFKFB3) expression is tightly correlated with multiple steps of tumorigenesis; however, the pathological significance of PFKFB3 in macrophages in patients with rheumatoid arthritis (RA) remains obscure. In this study, we examined whether PFKFB3 modulates macrophage activation and promotes RA development.
Method: Peripheral blood mononuclear cells (PBMCs) from patients with RA, THP-1 cells, and bone marrow-derived macrophages from conditional PFKFB3-knockout mice were used to investigate the mechanism underlying PFKFB3-induced macrophage regulation of RA.
Mol Genet Metab Rep
March 2025
The Shmunis School of Biomedicine and Cancer Research, The George S. Wise Faculty for Life Sciences, Sagol School of Neurosciences, Tel Aviv University, 6997801 Tel Aviv, Israel.
Dihydrolipoamide dehydrogenase (DLD) deficiency is an autosomal recessive disorder characterized by a functional disruption in several critical mitochondrial enzyme complexes, including pyruvate dehydrogenase and α-ketoglutarate dehydrogenase. Despite DLD's pivotal role in cellular energy metabolism, detailed molecular and metabolic consequences of DLD deficiency (DLDD) remain poorly understood. This study represents the first in-depth multi-omics analysis, specifically metabolomic and transcriptomic, of fibroblasts derived from a DLD-deficient patient compound heterozygous for a common Ashkenazi Jewish variant (c.
View Article and Find Full Text PDFMolecules
December 2024
Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, Yamagata 990-9585, Japan.
Leucine, isoleucine, and valine are collectively known as branched chain amino acids (BCAAs) and are often discussed in the same physiological and pathological situations. The two consecutive initial reactions of BCAA catabolism are catalyzed by the common enzymes referred to as branched chain aminotransferase (BCAT) and branched chain α-keto acid dehydrogenase (BCKDH). BCAT transfers the amino group of BCAAs to 2-ketoglutarate, which results in corresponding branched chain 2-keto acids (BCKAs) and glutamate.
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