Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.3.14 (ATP synthase)
7,042 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Skeletal muscle fibres of untrained animals experience a stress response following exercise. This study was aimed at investigating whether chronic exercise modulates stress proteins of 70 kDa (HSP70s) in skeletal muscle. In the soleus muscle of Wistar rats, adherence to an incremental programme of treadmill running (IPTR) of 3 months duration up-regulated the levels of the beta-subunit of the mitochondrial F1-ATPase and those of HSP72, GRP75 and GRP78. Neither beta-F1-ATPase nor sarcoplasmic reticulum Ca2+-ATPase levels changed with training in the extensor digitorum longus (EDL) muscle. However, HSP70s increased during training. In soleus muscle slices of animals sacrificed 3 days after completing the IPTR, HSP72 and GRP75 were synthesized at lower rates than in sedentary animals while the GRP78 synthesis rate increased. Trained, rested animals also experienced a stress response following acute exercise of lower intensity than that of the actual training sessions. The data suggest that up-regulation of HSP70s by chronic exercise depends upon continued physical activity. Furthermore, the inverse correlation between levels and rates of synthesis of HSP72 during rest periods suggests the operation of a feedback regulatory loop aimed at reestablishing the threshold levels characteristic of unstressed fibres.
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PMID:Stress proteins of 70 kDa in chronically exercised skeletal muscle. 1086 96

Changes in mitochondrial and sarcoplasmic proteins using proteinomics and Western blotting in hearts from copper-deficient rats were explored in this study. Also, key enzymes that are involved in cardiac energy metabolism via glycolysis and fatty acid oxidation and related transcription factors were determined. Rats were fed one of two diets: a copper-adequate diet containing 6 mg Cu/kg diet or a diet with less than 1 mg Cu/kg diet for 5 weeks. Copper deficiency was confirmed by low liver copper levels, decreased hematocrit levels and cardiac hypertrophy. Proteinomic data revealed that of the more than 50 proteins identified from the mitochondrial fraction of heart tissue, six were significantly down-regulated and nine were up-regulated. The proteins that were decreased were beta enolase 3, carbonic anhydrase 2, aldose reductase 1, glutathione peroxidase, muscle creatine kinase and mitochondrial aconitase 2. The proteins that were up-regulated were isocitrate dehydrogenase, dihydrolipoamide dehydrogenase, transferrin, subunit d of ATP synthase, transthyretin, preproapolipoprotein A-1, GRP 75, alpha-B crystalline and heat shock protein alpha. Follow-up Western blots on rate-limiting enzymes in glycolysis (phosphofructose kinase), fatty acid oxidation (medium chain acyl dehydrogenase, peroxisome proliferator-actvator receptor-alpha or PPARalpha) and gluconeogenesis (phosphoenolpyruvate carboxykinase) did not reveal changes in metabolic enzymes. However, a significant increase in peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha protein, as well as the transcript, which increased 2.5-fold, was observed. It would appear that increased mitochondrial biogenesis known to occur in copper deficiency hearts is caused by an increased expression in the master regulator of mitochondrial biogenesis, PGC-1alpha.
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PMID:Mitochondrial and sarcoplasmic protein changes in hearts from copper-deficient rats: up-regulation of PGC-1alpha transcript and protein as a cause for mitochondrial biogenesis in copper deficiency. 1899 53

Regulation of intracellular Ca(2+) concentration is critical in numerous biological processes. Inositol 1,4,5-trisphosphate receptor (IP3R) functions as the Ca(2+) release channel on endoplasmic reticulum (ER) membranes. Much attention has been dedicated to mitochondrial Ca(2+) uptake via mitochondria-associated ER membranes (MAM) which is involved in intracellular Ca(2+) homeostasis; however, the molecular mechanisms that link the MAM to mitochondria still remain elusive. We previously reported that Tespa1 (thymocyte-expressed, positive selection-associated gene 1) expressed in lymphocytes physically interacts with IP3R. In this study, we first performed double-immunocytochemical staining of Tespa1 with a mitochondrial marker or an ER marker on an acute T lymphoblastic leukemia cell line, Jurkat cells, by using anti-ATP synthase or anti-calnexin antibody, respectively, and demonstrated that Tespa1 was localized very close to mitochondria and the Tespa1 localization was overlapped with restricted portion of ER. Next, we examined the effects of Tespa1 on the T cell receptor (TCR) stimulation-induced Ca(2+) flux by using Ca(2+) imaging in Jurkat cells. Reduction of Tespa1 protein by Tespa1-specific siRNA diminished TCR stimulation-induced Ca(2+) flux into both mitochondria and cytoplasm through the analyses of the mitochondrial Ca(2+) indicator (Rhod-2) and the cytoplasmic Ca(2+) indicator (Fluo-4), respectively. Furthermore, co-immunoprecipitation assay in HEK293 cells revealed that exogenous Tespa1 protein physically interacted with a MAM-associated protein, GRP75 (glucose-regulated protein 75), but not with an outer mitochondrial membrane protein, VDAC1 (voltage-dependent anion channel 1). All these results suggested that Tespa1 will participate in the molecular link between IP3R-mediated Ca(2+) release and mitochondrial Ca(2+) uptake in the MAM compartment.
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PMID:Tespa1 is a novel component of mitochondria-associated endoplasmic reticulum membranes and affects mitochondrial calcium flux. 2350 Nov 3

MPV17 is an inner mitochondrial membrane protein whose mutation results in mitochondrial DNA (mtDNA) depletion diseases such as neurohepatopathy. MPV17 is expressed in several organs including the liver and kidneys. Here, we investigated its role and mechanism of action in cardiac ischemia/reperfusion (I/R) injury. Using isolated hearts from wild type and Mpv17 mutant (Mpv17^mut) mice, we found that mtDNA levels and normal cardiac function were similar between the groups. Furthermore, reactive oxygen species (ROS) generation, mitochondrial morphology, and calcium levels required to trigger mitochondrial permeability transition pore (mPTP) opening were all similar in normal/non-ischemic animals. However, following I/R, we found that mutant mice had poorer cardiac functional recovery and exhibited more mitochondrial structural damage. We also found that after I/R, Mpv17^mut heart mitochondria did not produce more ROS than wild type hearts but that calcium retention capacity was gravely compromised. Using immunoprecipitation and mass spectrometry, we identified ATP synthase, Cyclophilin D, MIC60 and GRP75 as proteins critical to mitochondrial cristae organization and calcium handling that interact with MPV17, and this interaction is reduced by I/R. Together our results suggest that MPV17 has a protective function in the heart and is necessary for recovery following insults to the heart.
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PMID:Inner mitochondrial membrane protein MPV17 mutant mice display increased myocardial injury after ischemia/reperfusion. 3277 9

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