Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.3.5.1 (succinate dehydrogenase)
 8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitochondria are dynamic intracellular organelles playing a central role in cell metabolism by generating ATP, through the oxidative phosphorylation system (OXPHOS). Altered mitochondrial functions have been identified as causative or contributing factors in some degenerative diseases and are becoming crucial to understanding cancer mechanisms. We report on distinct expression differences between mitochondria of normal and breast-infiltrating ductal carcinoma (IDC) cells. Mitochondria isolated from HMC (human mammary carcinoma) and HMEC (human mammary epithelial cell) cultures were assayed for expression levels of the multi-protein OXPHOS complexes using Western blot and densitometric analyses. Depressed expression levels were detected for all HMC OXPHOS complexes. Drastic signal reduction was observed for the succinate-dehydrogenase complex II iron-sulphur protein SDH-B (3.38%), while decreasing was reported for the NADH-ubiquinone oxidoreductase complex I Fe-S protein 3 NDUFS3 (32.78%) and the ubiquinol-cytochrome c reductase complex III protein 2 UQCRC2 (50.34%). A significant signal dropping was detected for the ATP-synthase complex V F(1)beta subunit (18.07%). For the cytochrome-oxidase complex IV (CO), near-depletion of the mitochondrial-encoded COI (4.37%) and no apparent variation of the COIV (97.26%) subunits were observed. CO and ATP-synthase were also assayed by cryo-immunoelectron microscopy (CIEM) on unfractionated HMC and HEMC cell mitochondria. COI and F(1)beta differential expression, invariance of COIV levels were corroborated, while HMC mitochondria morphology deterioration was highlighted. MitoTracker Red and fluorescence immunolabelling merging confirmed CIEM data. MitoTracker Red and Green co-staining showed mitochondria membrane property modulation. These data describe bioenergetic and phenotypic alterations of IDC cell mitochondria, possibly providing new cancer hallmarks.
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PMID:Alteration of expression levels of the oxidative phosphorylation system (OXPHOS) in breast cancer cell mitochondria. 1789 67

Rapamycin, an immunosuppressant used in human transplantation, impairs beta-cell function, but the mechanism is unclear. Chronic (24 h) exposure to rapamycin concentration dependently suppressed 16.7 mM glucose-induced insulin release from islets (1.65+/-0.06, 30 nM rapamycin versus 2.35+/-0.11 ng/islet per 30 min, control, n=30, P<0.01) without affecting insulin and DNA contents. Rapamycin also decreased alpha-ketoisocaproate-induced insulin release, suggesting reduced mitochondrial carbohydrate metabolism. ATP content in the presence of 16.7 mM glucose was significantly reduced in rapamycin-treated islets (13.42+/-0.47, rapamycin versus 16.04+/-0.46 pmol/islet, control, n=30, P<0.01). Glucose oxidation, which indicates the velocity of metabolism in the Krebs cycle, was decreased by rapamycin in the presence of 16.7 mM glucose (30.1+/-2.7, rapamycin versus 42.2+/-3.3 pmol/islet per 90 min, control, n=9, P<0.01). Immunoblotting revealed that the expression of complex I, III, IV, and V was not affected by rapamycin. Mitochondrial ATP production indicated that the respiratory chain downstream of complex II was not affected, but that carbohydrate metabolism in the Krebs cycle was reduced by rapamycin. Analysis of enzymes in the Krebs cycle revealed that activity of alpha-ketoglutarate dehydrogenase (KGDH), which catalyzes one of the slowest reactions in the Krebs cycle, was reduced by rapamycin (10.08+/-0.82, rapamycin versus 13.82+/-0.84 nmol/mg mitochondrial protein per min, control, n=5, P<0.01). Considered together, these findings indicate that rapamycin suppresses high glucose-induced insulin secretion from pancreatic islets by reducing mitochondrial ATP production through suppression of carbohydrate metabolism in the Krebs cycle, together with reduced KGDH activity.
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PMID:Rapamycin impairs metabolism-secretion coupling in rat pancreatic islets by suppressing carbohydrate metabolism. 1981 26