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

---

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

Thyroid hormone regulates the in vivo expression of a selected set of rat nuclear genes encoding mitochondrial inner membrane proteins. Certain mRNAs, such as that for cytochrome c1, are increased as much as 20-50-fold, while others, such as core protein 1 of Complex III and the F1-ATPase beta-subunit do not respond. The promoter region of human cytochrome c1 also supports thyroid hormone induction of a reporter gene in transient transfection experiments. Thus, thyroid hormone regulates only selected genes, even for subunits within the same complex and in widely varying species. By contrast, growth activation of quiescent NIH3T3 cells, a second paradigm used for stimulating mitochondrial biogenesis, does not increase cytochrome c1 mRNA but does increase F1-ATPase beta-subunit mRNA. These findings suggest that nuclear OXPHOS genes are not necessarily expressed in a coordinated manner, and that multiple regulatory circuits might exist which are linked to different physiological stimuli. Analysis of the promoters of several OXPHOS genes reveals a great diversity and heterogeneity of transfactor binding elements. No single regulatory feature exists which could account for a coordinated expression of all OXPHOS genes. The potential diversity for regulating expression of nuclear OXPHOS genes raises the possibility for the existence of disease states linked to regulatory defects.
...
PMID:The role of thyroid hormone and promoter diversity in the regulation of nuclear encoded mitochondrial proteins. 759 31

The transcript levels of nuclear and mitochondrial genes involved in oxidative phosphorylation were quantified in human myoblasts and myotubes cultured from biopsies of patients harboring either heteroplasmic point mutation or deletion of mitochondrial DNA. The transcript patterns were determined by two different methodologies, competitive reverse-transcription polymerase chain reaction and classical Northern blot analysis, both referred to the mitochondrial to nuclear DNA ratio. In myoblasts from the patients with MELAS (myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) and KSS (Kearns-Sayre) syndromes, both methodologies revealed an increase of mtDNA transcript levels. A higher level of the nuclear ATP synthase beta transcript was observed in the MELAS patient cells and could be the consequence of a feedback effect of the mitochondrial DNA mutation. Moreover, the nuclear and mitochondrial transcript accumulation is more pronounced after myoblast differentiation. Thus, the OXPHOS expression is specifically altered in patients with mitochondrial diseases. The competitive RT-PCR, a rapid and sensitive technique, could be applied to investigation of mitochondrial myopathies.
...
PMID:Quantification of OXPHOS gene transcripts during muscle cell differentiation in patients with mitochondrial myopathies. 988 18

To gain insight into the role of the general transcription factor, Sp1, in the expression of nuclear genes involved in mitochondrial biogenesis, we investigated Sp1 activation of the adenine nucleotide translocator 2, cytochrome c1, F1-ATPase beta subunit, and the mitochondria transcription factor (mtTFA) promoters transfected into Drosophila cell lines. The numbers and organization of GC elements vary in the four promoters, but the magnitude of activation by coexpressed human Sp1 was similar. A feature common to the four promoters is the presence of multiple, proximal Sp1-activating elements that account for 50% or more of the transcription activation by Sp1. The distribution and function of individual distal Sp1 elements is less defined and appear to be more promoter-specific. Finally, data from transfected Drosophila cells provide the first direct proof for the involvement of Sp1 in the negative regulation of the ANT2 promoter and as a possible participant in repression of the beta-subunit promoter. The role of Sp1 in both the positive and negative regulation of OXPHOS promoters is unique.
...
PMID:On the role of the general transcription factor Sp1 in the activation and repression of diverse mammalian oxidative phosphorylation genes. 1044 39

Diabetes-prone BHE/Cdb and Sprague-Dawley (SD) rats were studied with respect to mitochondrial (mt) function and mt gene expression. The BHE/Cdb rats carry mutations in the mt ATPase 6 gene that phenotype as decreased OXPHOS efficiency with subsequent development of impaired glucose tolerance. The base substitutions result in amino acid substitutions in the proton channel and this, in turn, affects the efficiency of energy capture in the ATP molecule. Feeding studies showed that BHE/Cdb rats required 10 times more vitamin E and three times more vitamin A in their diets than do normal SD rats. Vitamin A supplementation 'normalized' mt OXPHOS as well as increased the amount of ATPase subunit a protein in the mt compartment. Western blot analysis of retinoic acid receptors in the mitochondrial and nuclear compartments showed that these proteins were present in the mt compartment. The effect of the vitamin A supplementation plus the observation of retinoic acid receptors suggest that vitamin A functions to enhance the transcription of the ATPase 6 gene. Work with primary cultures of hepatocytes showed that not only does retinoic acid increase mitochondrial ATPase 6 gene expression but so too does the steroid hormone intermediate, dehydroepiandrosterone (DHEA). Triiodothyronine also plays a role in this process but not as an independent factor. Rather, this hormone potentiates the effects of retinoic acid and DHEA on ATPase gene expression. These results suggest that mt gene expression requires more than just the mt transcription factor A. More than likely the process requires a number of factors in much the same way as does nuclear gene expression.
...
PMID:Role of vitamin A in mitochondrial gene expression. 1173 5

Respiratory chain supercomplexes have been isolated from mammalian and yeast mitochondria, and bacterial membranes. Functional roles of respiratory chain supercomplexes are catalytic enhancement, substrate channelling, and stabilization of complex I by complex III in mammalian cells. Bacterial supercomplexes are characterized by their relatively high detergent-stability compared to yeast or mammalian supercomplexes that are stable to sonication. The mobility of substrate cytochrome c increases in the order bacterial, yeast, and mammalian respiratory chain. In bacterial supercomplexes, the electron transfer between complexes III and IV involves movement of the mobile head of a tightly bound cytochrome c, whereas the yeast S. cerevisiae seems to use substrate channelling of a mobile cytochrome c, and mammalian respiratory chains have been described to use a cytochrome c pool. Dimeric ATP synthase seems to be specific for mitochondrial OXPHOS systems. Monomeric complex V was found in Acetobacterium woodii and Paracoccus denitrificans.
...
PMID:Respiratory chain supercomplexes. 1179 23

To investigate the integrated evolution of mitochondrial and nuclear genomes in the eukaryotic cell, we have focused our attention on OXPHOS (oxidative phosphorylation) gene families which encode proteins involved in the main mitochondrial function. The present study reports the phylogenetic analysis of two OXPHOS gene families: ATP synthase subunit c (or lipid binding protein, LBP) and Cytochrome c (Cytc). Both gene families possess a higher expansion trend than the typically low duplication rate of OXPHOS genes in Metazoa, but follow a completely different evolutionary history, especially in mammals. LBP is represented by three well conserved isoforms in all mammals (P1, P2, P3): only P3 possesses a clearly conserved isoform in all Vertebrates, P1 and P2 were already present before the bird-mammal divergence and there are preliminary evidence from the in silico analysis that P1, the most evolutionary divergent isoform, is poorly expressed and not regulated by NRF1. In contrast, Cytc family presents at least two duplicated genes in all the analysed Vertebrates, is subject to a high expansion trend, especially of processed pseudogenes in mammals, and some events of gain and loss of function can be supposed.
...
PMID:Evolution of ATP synthase subunit c and cytochrome c gene families in selected Metazoan classes. 1646 Aug 89

F(1)F(0) ATP synthase is ectopically expressed on the surface of several cell types, including endothelium and cancer cells. This study uses immunocytochemical detection methods via highly specific monoclonal antibodies to explore the possibility of plasma membrane localization of other mitochondrial proteins using an osteosarcoma cell line in which the location of the mitochondrial reticulum can be clearly traced by green fluorescent protein tagging of the organelle. We found that subunits of three of the four respiratory chain complexes were present on the surface of these cells. Additionally, we show for the first time that F(0) subunits d and OSCP of the ATP synthase are ectopically expressed. In all cases the OXPHOS proteins show a punctate distribution, consistent with data from proteome analysis of isolated lipid rafts that place the various mitochondrial proteins in plasma membrane microdomains. We also examined the cell surface for marker membrane proteins from several other intracellular organelles including ER, golgi and nuclear envelope. They were not found on the surface of the osteosarcoma cells. We conclude that mitochondrial membrane proteins are ectopically expressed, but not proteins from other cellular organelles. A specific mechanism by which the mitochondrion and plasma membrane fuse to deliver organellar proteins is suggested.
...
PMID:The F(1)F(0) ATP synthase and mitochondrial respiratory chain complexes are present on the plasma membrane of an osteosarcoma cell line: An immunocytochemical study. 1711 62

Nowadays, we are facing a renaissance of mitochondria in cancer biology. However, our knowledge of the basic cell biology and on the timing and mechanisms that control the biosynthesis of mitochondrial constituents during progression through the cell cycle of mammalian cells remain largely unknown. Herein, we document the in vivo changes on mitochondrial morphology and dynamics that accompany cellular mitosis, and illustrate the following key points of the biogenesis of mitochondria during progression of liver cells through the cycle: (i) the replication of nuclear and mitochondrial genomes is synchronized during cellular proliferation, (ii) the accretion of OXPHOS proteins is asynchronously regulated during proliferation being the synthesis of beta-F1-ATPase and Hsp60 carried out also at G2/M and, (iii) the biosynthesis of cardiolipin is achieved during the S phase, although full development of the mitochondrial membrane potential (DeltaPsim) is attained at G2/M. Furthermore, we demonstrate using reporter constructs that the mechanism regulating the accretion of beta-F1-ATPase during cellular proliferation is controlled at the level of mRNA translation by the 3'UTR of the transcript. The 3'UTR-driven synthesis of the protein at G2/M is essential for conferring to the daughter cells the original phenotype of the parental cell. Our findings suggest that alterations on this process may promote deregulated beta-F1-ATPase expression in human cancer.
...
PMID:Biogenesis and dynamics of mitochondria during the cell cycle: significance of 3'UTRs. 1720 11

Analysis of the protein profile of mitochondria and its age-dependent variation is a promising approach to unravel mechanisms involved in aging and age-related diseases. Our studies focus on the mammalian mitochondrial membrane proteome, especially of the inner mitochondrial membrane with the respiratory chain complexes and other proteins possibly involved in life-span control and aging. Variations of the mitochondrial proteome during aging, with the emphasis on the abundance, composition, structure, and activity of membrane proteins, are examined in various rat tissues by native polyacrylamide gel electrophoresis techniques in combination with MALDI-TOF mass spectrometry. In rat brain, age-modulated differences in the abundance of various mitochondrial and nonmitochondrial proteins, such as Na,K-ATPase, HSP60, mitochondrial aconitase-2, V-type ATPase, MF(o)F(1) ATP synthase, and the OXPHOS complexes I-IV are detected. During aging, a decrease in the amount of intact MF(o)F(1) ATP synthase occurs in the cortex. As analytical technique, native PAGE separates not only individual proteins but also multi-subunit (membrane) proteins, (membrane) protein supercomplexes as well as interacting proteins in their native state. It reveals the occurrence and architecture of supramolecular assemblies of proteins. The age-related alterations in the oligomerization of the MF(o)F(1) ATP synthase observed by us in rat cortex might be one clue for understanding the link between respiration and longevity. Also, the abundance of OXPHOS supercomplexes, that is, the natural assemblies of the respiratory complexes I, III, and IV into supramolecular stoichiometric entities, such as I(1)III(2)IV(0-4), can differ between young and aged cortex tissue. Age-related changes in the supramolecular architecture of OXPHOS complexes might explain alterations in ROS production during aging.
...
PMID:Proteome alterations in rat mitochondria caused by aging. 1746 Jan 90

The impact of point mutations in mitochondrial tRNA genes on the amount and stability of respiratory chain complexes and ATP synthase (OXPHOS) has been broadly characterized in cultured skin fibroblasts, skeletal muscle samples, and mitochondrial cybrids. However, less is known about how these mutations affect other tissues, especially the brain. We have compared OXPHOS protein deficiency patterns in skeletal muscle mitochondria of patients with Leigh (8363G>A), MERRF (8344A>G), and MELAS (3243A>G) syndromes. Both mutations that affect mt-tRNA(Lys) (8363G>A, 8344A>G) resulted in severe combined deficiency of complexes I and IV, compared to an isolated severe defect of complex I in the 3243A>G sample (mt-tRNA(LeuUUR). Furthermore, we compared obtained patterns with those found in the heart, frontal cortex, and liver of 8363G>A and 3243A>G patients. In the frontal cortex mitochondria of both patients, the patterns of OXPHOS deficiencies differed substantially from those observed in other tissues, and this difference was particularly striking for ATP synthase. Surprisingly, in the frontal cortex of the 3243A>G patient, whose ATP synthase level was below the detection limit, the assembly of complex IV, as inferred from 2D-PAGE immunoblotting, appeared to be hindered by some factor other than the availability of mtDNA-encoded subunits.
...
PMID:The impact of mitochondrial tRNA mutations on the amount of ATP synthase differs in the brain compared to other tissues. 1831 67


1 2 3 Next >>

---