-
Journal of Bacteriology Dec 1986Light-induced ATP synthesis was studied in intact cells and chromatophores of Erythrobacter sp. strain OCh114. ATP synthesis was measured by both the pH method and the...
Light-induced ATP synthesis was studied in intact cells and chromatophores of Erythrobacter sp. strain OCh114. ATP synthesis was measured by both the pH method and the luciferin-luciferase luminescence method. The rate of ATP synthesis was moderate (a typical value of 0.65 mol of ATP per mol of bacteriochlorophyll per min), and synthesis was inhibited by antimycin A. ATP was synthesized under illumination only under aerobic conditions and not under anaerobic conditions. This characteristic was similar to that of other light-induced energy transduction processes in this bacterial species, such as oxidation of reaction center, oxidation of cytochrome c551, and translocation of H+, which were not observed under anaerobic conditions. This phenomenon was reconciled with the fact that the Erythrobacter sp. could not grow anaerobically even in the light. The characteristics of oxidative phosphorylation and ATP hydrolysis were also investigated. The respiratory ratio of chromatophores was 2.3. Typical rates of oxidative phosphorylation by NADH and by succinate were 2.9 mol of ATP per mol of bacteriochlorophyll per min (P/O = 0.22) and 1.1 mol of ATP per mol of bacteriochlorophyll per min (P/O = 0.19), respectively. A typical rate of ATP hydrolysis was 0.25 mol of ATP per mol of bacteriochlorophyll per min in chromatophores. ATPase and adenylate kinase are also involved in the metabolism of adenine nucleotides in this bacterium.
Topics: Adenosine Triphosphate; Aerobiosis; Antimycin A; Bacteria; Bacteriochlorophylls; Chromatophores; Light; Oxidative Phosphorylation; Oxygen; Photophosphorylation
PubMed: 3782035
DOI: 10.1128/jb.168.3.1142-1146.1986 -
American Journal of Respiratory Cell... Feb 2020
Topics: Cytokines; Glycolysis; Humans; Inflammation; Lipopolysaccharides; Macrophages, Alveolar; Oxidative Phosphorylation
PubMed: 31560565
DOI: 10.1165/rcmb.2019-0329ED -
International Immunopharmacology Sep 2022Interleukin-6 (IL-6) is a highly pleiotropic glycoprotein factor that can modulate innate and adaptive immunity as well as various aspects of metabolism, including... (Review)
Review
Interleukin-6 (IL-6) is a highly pleiotropic glycoprotein factor that can modulate innate and adaptive immunity as well as various aspects of metabolism, including glycolysis, fatty acid oxidation and oxidative phosphorylation. Recently, the expression and release of IL-6 is shown to be significantly increased in numerous diseases related to virus infection, and this increase is positively correlated with the disease severity. Immunity and metabolism are two highly integrated and interdependent systems, the balance between them plays a pivotal role in maintaining body homeostasis. IL-6-elicited inflammatory response is found to be closely associated with metabolic disorder in patients with viral infection. This brief review summarizes the regulatory role of IL-6 in immunometabolic reprogramming among seven viral infection-associated diseases.
Topics: Adaptive Immunity; COVID-19; Communicable Diseases; Glycolysis; Humans; Interleukin-6; Oxidative Phosphorylation
PubMed: 35780641
DOI: 10.1016/j.intimp.2022.109005 -
Environmental Toxicology and Chemistry Nov 2021This report describes a novel adverse outcome pathway (AOP) on uncoupling of oxidative phosphorylation (OXPHOS) leading to growth inhibition via decreased adenosine...
This report describes a novel adverse outcome pathway (AOP) on uncoupling of oxidative phosphorylation (OXPHOS) leading to growth inhibition via decreased adenosine triphosphate (ATP) pool and cell proliferation (AOPWiki, AOP263). Oxidative phosphorylation is a major metabolic process that produces the primary form of energy (ATP) supporting various biological functions. Uncoupling of OXPHOS is a widely recognized mode of action of many chemicals and is known to affect growth via different biological processes. Capturing these events in an AOP can greatly facilitate mechanistic understanding and hazard assessment of OXPHOS uncouplers and growth regulators in eukaryotes. The four proposed key events in this AOP are intentionally generalized to cover a wide range of organisms and stressors. Three out of four events can be measured using in vitro high-throughput bioassays, whereas for most organisms, growth inhibition can also be measured in a high-throughput format using standard in vivo toxicity test protocols. The key events and key event relationships in this AOP are further assessed for weight of evidence using evolved Bradford-Hill considerations. The overall confidence levels range from moderate to high with only a few uncertainties and inconsistencies. The chemical applicability domain of the AOP mainly contains protonophores uncouplers, which can be predicated using the quantitative structure-activity relationship (QSAR) approach and validated using in vitro high-throughput bioassays. The biological domain of the AOP basically covers all eukaryotes. The AOP described in this report is part of a larger AOP network linking uncoupling of OXPHOS to growth inhibition, and is considered highly relevant and applicable to both human health and ecological risk assessments.
Topics: Adenosine Triphosphate; Adverse Outcome Pathways; Biological Phenomena; Cell Proliferation; Humans; Oxidative Phosphorylation; Risk Assessment
PubMed: 34416019
DOI: 10.1002/etc.5197 -
Cancer Cell Nov 2018In this issue of Cancer Cell, Jones et al. demonstrate that LSCs are metabolically inflexible. LSCs rely on amino acid metabolism to fuel oxidative phosphorylation and...
In this issue of Cancer Cell, Jones et al. demonstrate that LSCs are metabolically inflexible. LSCs rely on amino acid metabolism to fuel oxidative phosphorylation and cannot compensate with other fuel sources following amino acid depletion. Combined venetoclax and azacitidine reduces amino acid uptake, partly explaining the anti-LSC effects.
Topics: Amino Acids; Humans; Leukemia, Myeloid, Acute; Neoplastic Stem Cells; Oxidative Phosphorylation
PubMed: 30423291
DOI: 10.1016/j.ccell.2018.10.012 -
Neoplasia (New York, N.Y.) 2000Hepatocyte growth factor/scatter factor (HGF/SF) is a paracrine growth factor which increases cellular motility and has also been implicated in tumor development and...
Hepatocyte growth factor/scatter factor (HGF/SF) is a paracrine growth factor which increases cellular motility and has also been implicated in tumor development and progression and in angiogenesis. Little is known about the metabolic alteration induced in cells following Met-HGF/SF signal transduction. The hypothesis that HGF/SF alters the energy metabolism of cancer cells was investigated in perfused DA3 murine mammary cancer cells by nuclear magnetic resonance (NMR) spectroscopy, oxygen and glucose consumption assays and confocal laser scanning microscopy (CLSM). 31P NMR demonstrated that HGF/SF induced remarkable alterations in phospholipid metabolites, and enhanced the rate of glucose phosphorylation (P < .05). 13C NMR measurements, using [13C1]-glucose-enriched medium, showed that HGS/SF reduced the steady state levels of glucose and elevated those of lactate (P < .05). In addition, HGF/SF treatment increased oxygen consumption from 0.58+/-0.02 to 0.71+/-0.03 micromol/hour per milligram protein (P < .05). However, it decreased CO2 levels, and attenuated pH decrease. The mechanisms of these unexpected effects were delineated by CLSM, using NAD(P)H fluorescence measurements, which showed that HGF/SF increased the oxidation of the mitochondrial NAD system. We propose that concomitant with induction of ruffling, HGF/SF enhances both the glycolytic and oxidative phosphorylation pathways of energy production.
Topics: Adenocarcinoma; Animals; Female; Glucosephosphates; Glycolysis; Hepatocyte Growth Factor; Mammary Neoplasms, Experimental; Mice; Models, Biological; NAD; NADP; Oxidative Phosphorylation; Phospholipids; Signal Transduction; Tumor Cells, Cultured
PubMed: 11005571
DOI: 10.1038/sj.neo.7900103 -
BMC Genomics Oct 2019We have previously reported on paucity of mitochondrial DNA (mtDNA) haplogroups J and K among Finnish endurance athletes. Here we aimed to further explore differences in...
BACKGROUND
We have previously reported on paucity of mitochondrial DNA (mtDNA) haplogroups J and K among Finnish endurance athletes. Here we aimed to further explore differences in mtDNA variants between elite endurance and sprint athletes. For this purpose, we determined the rate of functional variants and the mutational load in mtDNA of Finnish athletes (n = 141) and controls (n = 77) and determined the sequence variation in haplogroups.
RESULTS
The distribution of rare and common functional variants differed between endurance athletes, sprint athletes and the controls (p = 0.04) so that rare variants occurred at a higher frequency among endurance athletes. Furthermore, the ratio between rare and common functional variants in haplogroups J and K was 0.42 of that in the remaining haplogroups (p = 0.0005). The subjects with haplogroup J and K also showed a higher mean level of nonsynonymous mutational load attributed to common variants than subjects with the other haplogroups. Interestingly, two of the rare variants detected in the sprint athletes were the disease-causing mutations m.3243A > G in MT-TL1 and m.1555A > G in MT-RNR1.
CONCLUSIONS
We propose that endurance athletes harbor an excess of rare mtDNA variants that may be beneficial for oxidative phosphorylation, while sprint athletes may tolerate deleterious mtDNA variants that have detrimental effect on oxidative phosphorylation system. Some of the nonsynonymous mutations defining haplogroup J and K may produce an uncoupling effect on oxidative phosphorylation thus favoring sprint rather than endurance performance.
Topics: Athletes; DNA, Mitochondrial; Finland; Mutation; Oxidative Phosphorylation
PubMed: 31664900
DOI: 10.1186/s12864-019-6171-6 -
Scientific Reports Oct 2018Anticancer drug resistance is a major challenge of cancer therapy. We found that irinotecan-resistant NSCLC cells showed increased mitochondrial oxidative...
Anticancer drug resistance is a major challenge of cancer therapy. We found that irinotecan-resistant NSCLC cells showed increased mitochondrial oxidative phosphorylation compared to the drug sensitive NSCLC cells. Previously, we found that combined inhibition of aldehyde dehydrogenase using gossypol, and mitochondrial complex I using phenformin, effectively reduced oxidative phosphorylation in NSCLC. Here, we showed that targeting oxidative phosphorylation with gossypol and phenformin abrogated irinotecan resistance in NSCLC. Furthermore, irinotecan treatment by blocking oxidative phosphorylation induced synergistic anti-cancer effect in NSCLC. The pre-clinical xenograft model of human NSCLC also demonstrated a therapeutic response to the dual targeting treatment. Therefore, this combination of gossypol and phenformin increases irinotecan sensitivity as well as preventing irinotecan resistance.
Topics: Animals; Carcinoma, Non-Small-Cell Lung; Cell Death; Cell Line, Tumor; Drug Resistance, Neoplasm; Drug Synergism; Gossypol; Heterografts; Humans; Irinotecan; Mice; Mitochondria; Oxidative Phosphorylation; Phenformin
PubMed: 30356107
DOI: 10.1038/s41598-018-33667-6 -
International Journal of Molecular... Jun 2022Mitochondrial dysfunction is a pathophysiological hallmark of most neurodegenerative diseases. Several clinical trials targeting mitochondrial dysfunction have been... (Review)
Review
Mitochondrial dysfunction is a pathophysiological hallmark of most neurodegenerative diseases. Several clinical trials targeting mitochondrial dysfunction have been performed with conflicting results. Reliable biomarkers of mitochondrial dysfunction in vivo are thus needed to optimize future clinical trial designs. This narrative review highlights various neuroimaging methods to probe mitochondrial dysfunction. We provide a general overview of the current biological understanding of mitochondrial dysfunction in degenerative brain disorders and how distinct neuroimaging methods can be employed to map disease-related changes. The reviewed methodological spectrum includes positron emission tomography, magnetic resonance, magnetic resonance spectroscopy, and near-infrared spectroscopy imaging, and how these methods can be applied to study alterations in oxidative phosphorylation and oxidative stress. We highlight the advantages and shortcomings of the different neuroimaging methods and discuss the necessary steps to use these for future research. This review stresses the importance of neuroimaging methods to gain deepened insights into mitochondrial dysfunction in vivo, its role as a critical disease mechanism in neurodegenerative diseases, the applicability for patient stratification in interventional trials, and the quantification of individual treatment responses. The in vivo assessment of mitochondrial dysfunction is a crucial prerequisite for providing individualized treatments for neurodegenerative disorders.
Topics: Humans; Neurodegenerative Diseases; Neuroimaging; Oxidative Phosphorylation; Oxidative Stress; Positron-Emission Tomography
PubMed: 35806267
DOI: 10.3390/ijms23137263 -
European Journal of Biochemistry Aug 1980A phenomenological theory considering the output characteristics of oxidative phosphorylation has been worked out by adopting the formalism of linear nonequilibrium...
A phenomenological theory considering the output characteristics of oxidative phosphorylation has been worked out by adopting the formalism of linear nonequilibrium thermodynamics. The linearity of oxidative phosphorylation in the range of the output forces of practical interest has been experimentally verified. the efficiency of oxidative phosphorylation is zero if either a load with a zero conductance (open-circuited situation) or a load with an infinite conductance (short-circuited situation) is attached to oxidative phosphorylation. In between these extreme conductances there exists a finite load conductance permitting oxidative phosphorylation to operate with optimal efficiency. The necessary and sufficient condition for optimal efficiency was found to be L33/L11 = square root 1 - q2 where L11 is the phenomenological conductance of phosphorylation, L33 the phenomenological conductance of the load and q the degree of coupling of oxidative phosphorylation driven by respiration. This condition was called conductance matching. Under the condition of conductance matching, four output functions of oxidative phosphorylation of practical interest were optimized. A maximal net rate of oxidative phosphorylation occurs at a degree of coupling qf = 0.78. A maximal output power of oxidative phosphorylation, i.e. net rate times established phosphate potential, resuls at qp = 0.91. The maximization of the function net rate times efficiency yielded an economic degree of coupling qfec = 0.95 for maximal ATP flow. Finally, maximization of the function output power times efficiency led to a degree of coupling qpec = 0.97. This last function simultaneously maximized net rate of ATP production, developed phosphate potential and efficiency and reflects therefore the most economic solution to the output problem under the condition of conductance matching. In isolated rat livers perfused in a metabolic resting state, the condition of conductance matching is fulfilled. In addition, the degree of coupling oxidative phosphorylation under these conditions corresponds to the economic degree of coupling qpec.
Topics: Adenosine Triphosphate; Animals; Kinetics; Liver; Mathematics; Models, Biological; Oxidative Phosphorylation; Oxygen Consumption; Rats; Thermodynamics
PubMed: 7408881
DOI: 10.1111/j.1432-1033.1980.tb04792.x