Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.5.3 (complex I)
 8,901 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Skeletal muscle exhibits considerable variation in mitochondrial content among fiber types, but it is less clear whether mitochondria from different fiber types also present specific functional and regulatory properties. The present experiment was undertaken on ten 170-day-old pigs to compare functional properties and control of respiration by adenine nucleotides in mitochondria isolated from predominantly slow-twitch (Rhomboideus (RM)) and fast-twitch (Longissimus (LM)) muscles. Mitochondrial ATP synthesis, respiratory control ratio (RCR) and ADP-stimulated respiration with either complex I or II substrates were significantly higher (25-30%, P<0.05) in RM than in LM mitochondria, whereas no difference was observed for basal respiration. Based on mitochondrial enzyme activities (cytochrome c oxidase [COX], F0F1-ATPase, mitochondrial creatine kinase [mi-CK]), the higher ADP-stimulated respiration rate of RM mitochondria appeared mainly related to a higher maximal oxidative capacity, without any difference in the maximal phosphorylation potential. Mitochondrial K(m) for ADP was similar in RM (4.4+/-0.9 microM) and LM (5.9+/-1.2 microM) muscles (P>0.05) but the inhibitory effect of ATP was more marked in LM (P<0.01). These findings demonstrate that the regulation of mitochondrial respiration by ATP differs according to muscle contractile type and that absolute muscle oxidative capacity not only relies on mitochondrial density but also on mitochondrial functioning per se.
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PMID:Control of skeletal muscle mitochondria respiration by adenine nucleotides: differential effect of ADP and ATP according to muscle contractile type in pigs. 1564 76

Array technology has been increasingly used to monitor global gene expression patterns in various tissues and cell types. However, applications to muscle development and pathology as well as meat production in livestock species have been hampered by the lack of appropriate cDNA collections. To overcome this problem, a directed cDNA library was constructed starting from 23 muscles of meat-producing bovines to derive a collection of 3573 clones. A preliminary sequence characterization of this collection indicated that the most abundant transcripts correspond to genes encoding proteins involved in energy metabolism (COX and NADH dehydrogenase subunits) and belonging to the contractile apparatus (myosin chains and troponin isoforms). From this cDNA library, we selected a set of 435 clones representing 340 unique genes, of which 24 were novel. This collection was subsequently completed with 75 specific cDNA probes for genes of interest already studied in our laboratory. The bovine 'muscle' cDNA repertoire thus designed was spotted onto a nylon membrane (macroarray) in order to test its utility to further investigate the transcriptome of bovine muscles in relation to meat quality traits. It is also anticipated that this type of collection might be useful for the study of chronic myologic diseases in other mammalian species, including humans.
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PMID:A collection of bovine cDNA probes for gene expression profiling in muscle. 1565 21

Ovarian granulosa cells are known to play a key role in regulating ovarian physiology. Age increases apoptosis in follicular granulosa cells and subsequently decreases ovarian fecundity. The aging ovary also contains fewer follicles that possess fewer granulosa cells. The viability of follicular granulosa cells may be essential for development of the oocyte. Calcium ion plays an important role in a variety of biological processes, including gene expression, cell cycle regulation, and cell death. To study the ability of mitochondrial biogenesis in human granulosa cells, we determined the mitochondrial marker proteins, including the nuclear-encoded NADH-ubiquinone oxidoreductase alpha subunit 9 (NDUFA9) and mitochondrial-encoded COX I, after treatment of the cells with the calcium ionophore A23187. We showed that the expression of these mitochondrial marker proteins in human granulosa cells increased with changes in cytosolic Ca2+ using the ionophore A23187. Treatment of granulosa cells with 0.5 microM of A23187 for 120 h increased the levels of NDUFA 9 and COX I subunit by up to 2.6- and 2.4-fold, respectively. Raising Ca2+ by exposing granulosa cells to 1 microM of A23187 for 48 h significantly increased mitochondrial transcription factor (mtTFA) gene expression by up to 2.9-fold. Our results indicate that the adaptive responses of granulosa cells to increased Ca2+ may include upregulation of mitochondrial proteins and that mtTFA may be involved in such a mitochondrial biogenesis pathway.
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PMID:Calcium stimulates mitochondrial biogenesis in human granulosa cells. 1596 58

The barrier functions in epithelial and endothelial cells seem to be very important for maintaining normal biological homeostasis. However, it is unclear whether or how bile acids affect the epithelial barrier. We examined the bile acid-induced disruption of the epithelial barrier. We measured the transepithelial electrical resistance (TEER) of Caco-2 cells as a marker of disruption of the epithelial barrier. Reactive oxygen species (ROS) generation was also measured. Cholic acid (CA) decreased the TEER and increased intracellular ROS generation. PLA2 (phospholipase A2), COX (cyclooxygenase), PKC (protein kinase), ERK 1/2 (extracellular signal-regulated kinase 1/2), PI 3 K (phosphatidylinositol 3-kinase), p38 MAPK (p38 mitogen-activated protein kinase), MLCK (myosin light-chain kinase), NADH dehydrogenase, and XO (xanthine oxidase) inhibitors or ROS scavengers prevented the CA-induced TEER decrease. PLA2, COX, PKC, NADH dehydrogenase, and XO inhibitors prevented the CA-induced ROS generation but not ERK 1/2, PI 3 K, p38 MAPK, and MLCK inhibitors. If the cells were treated with ROS generators such as superoxide dismutase, the TEER decreased. ERK 1/2, PI 3 K, p38 MAPK, and MLCK inhibitors prevent these ROS generators from inducing the TEER decrease. These results suggest that ROS play an important role. In addition, PLA2, COX, PKC, NADH dehydrogenase, and XO are located upstream of the ROS generation, but ERK 1/2, PI 3 K, p38 MAPK, and MLCK are downstream during the signaling of CA-induced TEER alterations.
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PMID:Bile acid modulates transepithelial permeability via the generation of reactive oxygen species in the Caco-2 cell line. 1610 7

In spite of opposing changes in rates of adenosine triphosphate turnover, hypertrophy and atrophy of the heart are accompanied by the same changes in gene expression, resembling a fetal genotype. Fetal hearts are characterized by increased ischemia tolerance. We assessed respiratory capacity of mitochondrial subpopulations from unloaded and pressure-overloaded hearts before and after 15 minutes of normothermic ischemia. Unloading was achieved by heterotopic rat heart transplantation and overloading by aortic banding. Respiratory chain gene expression (NADH dehydrogenase, cytochrome c oxidase [COX]) were analyzed by reverse transcriptase-polymerase chain reaction. Subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM) were isolated by differential centrifugation. Citrate synthase was used as mitochondrial marker enzyme. Adenosine diphosphate-stimulated oxygen consumption (state 3) was measured with a Clark-type electrode. Unloading resulted in atrophy, overloading in hypertrophy. State 3 was reduced in atrophied hearts both in SSM and IFM (SSM: 204 +/- 79 vs 804 +/- 147 natoms oxygen min(-1) mL(-1), P < .001; IFM: 468 +/- 158 vs 1141 +/- 296 natoms oxygen min(-1) mL(-1), P < .05), but was unchanged in hypertrophied hearts. NADH dehydrogenase and COX expression was also decreased with atrophy and was unchanged with hypertrophy. Ischemia caused decreased recovery of citrate synthase in isolates of SSM (P < .05) but not of IFM. State 3 in control hearts was reduced in IFM (-41%, P < .01) and SSM (-19%, not significant). This ischemia-induced decrease was less pronounced in SSM (-2%) and IFM (-22%) of atrophied and IFM (-23%) of hypertrophied hearts. Subsarcolemmal mitochondria of hypertrophied hearts displayed the greatest ischemia-induced decrease of state 3 (-32%, P < .05). In conclusion, (1) long-term changes in workload differentially affect maximal respiratory capacity and ischemia tolerance of isolated mitochondria. The changes are not parallel to the changes in energy requirements. (2) Mitochondria of atrophied hearts appear to be more resistant against ischemia than controls.
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PMID:Differential changes in respiratory capacity and ischemia tolerance of isolated mitochondria from atrophied and hypertrophied hearts. 1683 47

We describe a 7-year-old girl who presented with loss of appetite, weakness and excercise intolerance. Enzyme investigation of the respiratory chain in muscle tissue revealed a combined complex I, III and IV deficiency. A novel heteroplasmic G-->A exchange at nucleotide position 14739 was found in the MTTE gene of the tRNA glutamic acid. The mutation load in muscle was 72%, urine sediment 38%, blood 31% and fibroblasts 29% and it correlated with COX-negative fibres. Our patient presented with a predominantly myopathic phenotype. The G14739A mutation is the third reported in the mitochondrial tRNA glutamic acid gene, and it occurred in a sporadic case.
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PMID:A novel sporadic mutation G14739A of the mitochondrial tRNA(Glu) in a girl with exercise intolerance. 1705 56

It has been documented that dietary copper (Cu) deficiency impairs mitochondrial respiratory function, which is catalyzed by 5 membrane-bound multiple protein complexes. However, there are few reports on the simultaneous analysis of Cu effect on the subunit protein expression on all 5 protein complexes. The present study was undertaken to determine the effect of Cu deficiency on each mitochondrial respiratory complex's protein expression in rat heart tissue with western-blot analysis. Male Sprague-Dawley rats were fed diets that were either Cu adequate (6.0 microg Cu/g diet, n = 5) or Cu deficient (0.3 microg Cu/g diet, n = 5) for 5 wk. The monoclonal antibody-based western-blot analysis suggested that the protein levels of 39-kDa and 30-kDa subunits in complex I; 70-kDa and 30-kDa subunits in complex II; core I and core II subunits in complex III; and alpha and beta subunits of F1 complex in complex V in both high-salt buffer (HSB) and low-salt buffer (LSB) protein fractions from heart tissue of Cu-deficient rats did not differ from those of Cu-adequate rats. However, the protein level of cytochrome c oxidase (CCO) subunit (COX) I, COX Vb, and COX VIb subunits in complex IV (CCO) in both HSB and LSB protein fractions from heart tissue of Cu-deficient rats was lower than those of Cu-adequate rats. Collectively, these data demonstrate that Cu deficiency decreases each tested subunit protein expression of complex IV but not those of complex I, II, III, and V in mitochondrial respiratory complexes.
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PMID:Copper deficiency decreases complex IV but not complex I, II, III, or V in the mitochondrial respiratory chain in rat heart. 1718 94

Increased nuclear protein O-linked beta-N-acetylglucosamine glycosylation (O-GlcNAcylation) mediated by high glucose treatment or the hyperglycemia of diabetes mellitus contributes to cardiac myocyte dysfunction. However, whether mitochondrial proteins in cardiac myocytes are also submitted to O-GlcNAcylation or excessive O-GlcNAcylation alters mitochondrial function is unknown. In this study, we determined if mitochondrial proteins are O-GlcNAcylated and explored if increased O-GlcNAcylation is linked to high glucose-induced mitochondrial dysfunction in neonatal rat cardiomyocytes. By immunoprecipitation, we found that several mitochondrial proteins, which are members of complexes of the respiratory chain, like subunit NDUFA9 of complex I, subunits core 1 and core 2 of complex III, and the mitochondrial DNA-encoded subunit I of complex IV (COX I) are O-GlcNAcylated. By mass spectrometry, we identified that serine 156 on NDUFA9 is O-GlcNAcylated. High glucose treatment (30 mm glucose) increases mitochondrial protein O-GlcNAcylation, including those of COX I and NDUFA9 which are reduced by expression of O-GlcNAcase (GCA). Increased mitochondrial O-GlcNAcylation is associated with impaired activity of complex I, III, and IV in addition to lower mitochondrial calcium and cellular ATP content. When the excessive O-GlcNAc modification is reduced by GCA expression, mitochondrial function improves; the activity of complex I, III, and IV increases to normal and mitochondrial calcium and cellular ATP content are returned to control levels. From these results we conclude that specific mitochondrial proteins of cardiac myocytes are O-GlcNAcylated and that exposure to high glucose increases mitochondrial protein O-GlcNAcylation, which in turn contributes to impaired mitochondrial function.
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PMID:Increased enzymatic O-GlcNAcylation of mitochondrial proteins impairs mitochondrial function in cardiac myocytes exposed to high glucose. 1900 14

Rearrangements of mitochondrial DNA in MSC16 mutant of cucumber (Cucumis sativus L.) affect mitochondrial functioning due to the alteration mainly of Complex I resulting in several metabolic changes. One-dimensional Blue-Native polyacrylamide gel electrophoresis (BN-PAGE) and densitometric measurements showed that the level and in-gel capacity of Complex I were lower in MSC16 leaf and root mitochondria as compared to wild-type (WT). The level and capacity of supercomplex I+III(2) were always lower in leaf but not in MSC16 root mitochondria. Two-dimensional BN/SDS-PAGE indicated that the band abundance for most of the subunits of Complex I was lower in MSC16 leaf and root mitochondria. Supercomplex I+III(2) level was only altered in MSC16 leaf mitochondria as measured after 2D BN/SDS-PAGE. No differences in the qualitative composition of the subunits of Complex I and supercomplex I+III(2) between MSC16 and WT mitochondria were observed. In MSC16 mitochondria Complex I impairment could be compensated to some extent by additional respiratory chain NADH dehydrogenases. A higher capacity and level of NDB-1 protein of external NADH dehydrogenase was observed in MSC16 leaf and root mitochondria as compared to WT. The level of COX II, mitochondrial-encoded subunit of Complex IV, was higher in MSC16 leaf and root mitochondria. However, the capacity of Complex IV was slightly higher only in MSC16 leaf mitochondria. The levels of complexes: III(2) and V and Complex V capacity did not differ in mitochondria between genotypes. An abundance of the subunits of respiratory complexes is one of the key factors determining not only their structure and functional stability but also a formation of the supercomplexes. We discuss here mitochondrial genome rearrangements in MSC16 mutant in a relation to assembly and/or stability (the lower level and capacity) of Complex I and supercomplex I+III(2).
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PMID:BN-PAGE analysis of the respiratory chain complexes in mitochondria of cucumber MSC16 mutant. 1918 34

We defined the transcriptomic and proteomic profiles of rat ageing skeletal muscle using a combined cDNA array, 2D- and Blue native-PAGE approach. This was allowed to obtain an overview of the interrelated events leading to the transcriptome/proteome/mitoproteome changes likely to underlie the structural/metabolic features of aged skeletal muscle. The main differences were found in genes/proteins related to energy metabolism, mitochondrial pathways, myofibrillar filaments, and detoxification. Concerning the abundance of mitochondrial OXPHOS complexes as well as their supramolecular organization and activity, mitochondria from old rats, when compared with those from young rats, contained significantly lower amounts of complex I (NADH:ubiquinone oxidoreductase), V (FoF1-ATP synthase), and III (ubiquinol:cytochrome c oxidoreductase). The same mitochondria contained a significantly larger amount of complex II (succinate:ubiquinone oxidoreductase), but an unchanged amount of complex IV (cytochrome c oxidase, COX). When comparing the supercomplex profiles between young and old muscle mitochondria, the densitometric analysis revealed that lighter supercomplexes were significantly reduced in older mitochondria, and that in the older group the major supercomplex bands were those representing heavier supercomplexes, likely suggesting a compensatory mechanism that, in ageing muscle, is functionally directed towards substrate channeling and catalytic enhancement advantaging the respirosome.
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PMID:Defining the transcriptomic and proteomic profiles of rat ageing skeletal muscle by the use of a cDNA array, 2D- and Blue native-PAGE approach. 1926 20


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