Search results for "respiratory chain"
showing 10 items of 96 documents
A spontaneous mitonuclear epistasis converging on Rieske Fe-S protein exacerbates complex III deficiency in mice
2020
We previously observed an unexpected fivefold (35 vs. 200 days) difference in the survival of respiratory chain complex III (CIII) deficient Bcs1lp.S78G mice between two congenic backgrounds. Here, we identify a spontaneous homoplasmic mtDNA variant (m.G14904A, mt-Cybp.D254N), affecting the CIII subunit cytochrome b (MT-CYB), in the background with short survival. We utilize maternal inheritance of mtDNA to confirm this as the causative variant and show that it further decreases the low CIII activity in Bcs1lp.S78G tissues to below survival threshold by 35 days of age. Molecular dynamics simulations predict D254N to restrict the flexibility of MT-CYB ef loop, potentially affecting RISP dyna…
Correction: DAPIT Over-Expression Modulates Glucose Metabolism and Cell Behaviour in HEK293T Cells
2015
Introduction Diabetes Associated Protein in Insulin-sensitive Tissues (DAPIT) is a subunit of mitochondrial ATP synthase and has also been found to associate with the vacuolar H+-ATPase. Its expression is particularly high in cells with elevated aerobic metabolism and in epithelial cells that actively transport nutrients and ions. Deletion of DAPIT is known to induce loss of mitochondrial ATP synthase but the effects of its over-expression are obscure. Results In order to study the consequences of high expression of DAPIT, we constructed a transgenic cell line that constitutively expressed DAPIT in human embryonal kidney cells, HEK293T. Enhanced DAPIT expression decreased mtDNA content and …
Chronic progressive external ophthalmoplegia with a novel mitochondrial DNA deletion and a mutation in the tRNALEU(UUR) gene
1999
Large-scale deletions and point mutations of the mitochondrial DNA are generally accepted as being involved in the pathogenesis of diseases associated with mitochondrial encephalomyopathies such as Kearns-Sayre syndrome and chronic progressive external ophthalmoplegia (CPEO). We screened suspected patients using polymerase chain reaction techniques, Southern blot analyses, and muscle biopsy specimens. We report on a novel 4,953-base pair deletion associated with a familial occurrence of a tRNA Leu(UUR) T3250C point mutation in a young female patient clinically diagnosed with CPEO. This deletion is not flanked by direct repeats, so slip replication and homologous recombination do not seem li…
Mitochondrial DNA mutations in cancer--from bench to bedside.
2009
Mitochondria are cell organelles mostly known for their production of ATP through oxidative phosphorylation. As suggested over 70 years ago by O. Warburg and recently confirmed with molecular techniques, alterations in respiratory activity and mitochondrial DNA appear to be a common feature of malignant cells. Somatic mtDNA mutations have been reported in many types of cancer cells. MtDNA mutation pattern may enhance the specificity of cancer diagnostics, detection and prediction of tumor growth rate and patients' outcome. Therefore it may be used as a molecular cancer bio-marker. Nevertheless recently published papers list a large number of mitochondrial DNA mutations in many different can…
Identification of a novel compound heterozygote SCO2 mutation in cytochrome c oxidase deficient fatal infantile cardioencephalomyopathy
2006
UNLABELLED Fatal infantile cardioencephalomyopathy (OMIM No. 604377) is a disorder of the mitochondrial respiratory chain and is characterised by neonatal progressive muscular hypotonia and cardiomyopathy because of severe Cytochrome c oxidase deficiency. Here we report a novel mutation in the Cytochrome c oxidase assembly gene SCO2 in an infant with fatal infantile cardioencephalomyopathy despite normal initial metabolic screening. CONCLUSION In newborns with unexplained muscular hypotonia and cardiomyopathy genetic testing of mitochondrial respiratory chain disorders might be helpful to establish a final diagnosis and guide treatment decisions.
Mitochondria and Ageing
2018
Mitochondria are the major sites of oxygen utilisation for energy production in cells. Indeed, all the reactions of the Krebs’ Cycle take place in mitochondria and they produce NADH and succinate, which are then oxidised in the respiratory chain. Experiments dating back to the early part of the twentieth century seemed to indicate that at a high rate of oxygen consumption (referred to gram of body weight) was normally associated with a low maximum lifespan. Thus, it was thought that it was the rate of oxygen utilisation that was related to “the rate of living”. However, more recent data pointed out that birds are unique because they combine high rates of oxygen consumption with a high maxim…
Kinetik der energieverbrauchenden Rückreaktion in der Atmungskette
1964
Die Kinetik der energieabhangigen Ruckreaktionen der Atmungskette wird fur die Atmungskettenkomponenten gemessen. Energiezufuhr wird durch Zusatz von ATP ausgelost. Die relative Geschwindigkeit der Ruckreaktion und der untersuchten Reaktionsschritte ist gleich gros (0,30 sec−1) bei 15°. Die Halbsattigungskonstante fur ATP in der Ruckreaktion ist 40 μM. Geschwindigkeitslimitierend fur die Ruckreaktion in der Atmungskette ist die Energieuberfuhrung von ATP. Die Hinreaktionen der Atmungskette, soweit sie zur Phosphorylierung gekoppelt ist, wird ebenfalls durch die Energieuberfuhrung auf ADP limitiert. Hohe Geschwindigkeiten der Hinreaktion lassen sich bei Entkopplung messen. Die Befunde deuten…
Tigliane diterpenes from the latex of Euphorbia obtusifolia with inhibitory activity on the mammalian mitochondrial respiratory chain
2003
Abstract Six diterpenes isolated from the latex of Euphorbia obtusifolia Poir. (Euphorbiaceae) were evaluated for their inhibition of the NADH oxidase activity in submitochondrial particles from beef heart. 4,20-Dideoxyphorbol-12,13-bis(isobutyrate) was the most potent inhibitor and showed an inhibitory concentration with IC 50 value of 2.6±0.3 mM. In the present study, some structure–activity trends are suggested for the inhibitory activity of the mammalian mitochondrial respiratory chain of these natural product derivatives of 4-deoxyphorbol esters.
Mitochondrial oxidative injury: a key player in nonalcoholic fatty liver disease.
2020
Nonalcoholic fatty liver disease (NAFLD) has become the most prevalent liver disease worldwide. NAFLD is tightly linked to the metabolic syndrome, insulin resistance, and oxidative stress. Globally, its inflammatory form, nonalcoholic steatohepatitis (NASH), has become the main cause of liver-related morbidity and mortality, mainly due to liver cirrhosis and primary liver cancer. One hallmark of NASH is the presence of changes in mitochondrial morphology and function that are accompanied by a blocked flow of electrons in the respiratory chain, which increases formation of mitochondrial reactive oxygen species in a self-perpetuating vicious cycle. Consequences are oxidation of DNA bases and …
Cellular Oxygen Concentration
1976
At low oxygen levels the intracellular or intramitochondrial concentration of molecular oxygen together with the amount of reduced cytochrome oxydase determines the rate of oxygen utilization. Below the so-called “critical oxygen concentration”, i.e. the value, at which a drop in the rate of oxygen uptake has its first evidence, the kinetic is described by the oxygen affinity (Km) of the respiratory chain, i.e. the concentration value for half maximal rate of oxygen uptake.