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- Identification, Expression, and Taxonomic Distribution of Alternative Oxidases in Non-Angiosperm Plants. [JOURNAL ARTICLE]
- Gene 2013 May 9.
Alternative oxidase (AOX) is a terminal ubiquinol oxidase present in the respiratory chain of all angiosperms investigated to date, but AOX distribution in other members of the Viridiplantae is less clear. We assessed the taxonomic distribution of AOX using bioinformatics. Multiple sequence alignments compared AOX proteins and examined amino acid residues involved in AOX catalytic function and post-translational regulation. Novel AOX sequences were found in both Chlorophytes and Streptophytes and we conclude that AOX is widespread in the Viridiplantae. AOX multigene families are common in non-angiosperm plants and the appearance of AOX1 and AOX2 subtypes pre-dates the divergence of the Coniferophyta and Magnoliophyta. Residues involved in AOX catalytic function are highly conserved between Chlorophytes and Streptophytes, while AOX post-translational regulation likely differs in these two lineages. We demonstrate experimentally that an AOX gene is present in the moss Physcomitrella patens and that the gene is transcribed. Our findings suggest that AOX will likely exert an influence on plant respiration and carbon metabolism in non-angiosperms such as green algae, bryophytes, liverworts, lycopods, ferns, gnetophytes, and gymnosperms and that further research in these systems is required.
- Unraveling the heater: new insights into the structure of the alternative oxidase. [Journal Article]
- Annu Rev Plant Biol 2013 Apr 29.:637-63.
The alternative oxidase is a membrane-bound ubiquinol oxidase found in the majority of plants as well as many fungi and protists, including pathogenic organisms such as Trypanosoma brucei. It catalyzes a cyanide- and antimycin-A-resistant oxidation of ubiquinol and the reduction of oxygen to water, short-circuiting the mitochondrial electron-transport chain prior to proton translocation by complexes III and IV, thereby dramatically reducing ATP formation. In plants, it plays a key role in cellular metabolism, thermogenesis, and energy homeostasis and is generally considered to be a major stress-induced protein. We describe recent advances in our understanding of this protein's structure following the recent successful crystallization of the alternative oxidase from T. brucei. We focus on the nature of the active site and ubiquinol-binding channels and propose a mechanism for the reduction of oxygen to water based on these structural insights. We also consider the regulation of activity at the posttranslational and retrograde levels and highlight challenges for future research.
- Ubiquinol supplementation enhances peak power production in trained athletes: a double-blind, placebo controlled study. [JOURNAL ARTICLE]
- J Int Soc Sports Nutr 2013 Apr 29; 10(1):24.
BACKGROUND:To investigate the effect of Ubiquinol supplementation on physical performance measured as maximum power output in young and healthy elite trained athletes.
METHODS:In this double-blind, placebo-controlled study, 100 young German well trained athletes (53 male, 47 female, age 19.9 +/- 2.3 years) received either 300 mg Ubiquinol or placebo for 6 weeks. Athletes had to perform a maximum power output test and the performance in W/kg of bodyweight was measured at the 4 mmol lactate threshold on a cycling ergometer before the supplementation treatment (T1), after 3 weeks (T2) and after 6 weeks (T3) of treatment. In these 6 weeks all athletes trained individually in preparation for the Olympic Games in London 2012. The maximum power output was measured in Watt/kilogram body weight (W/kg bw)
RESULTS:Both groups, placebo and Ubiquinol, significantly increased their physical performance measured as maximum power output over the treatment period from T1 to T3. The placebo group increased from 3.64 +/- 0.49 W/kg bw to 3.94 +/- 0.47 W/kg bw which is an increase of +0.30 +/- 0.18 W/kg bw or +8.5% (+/-5.7). The Ubiquinol group increased performance levels from 3.70 W/kg bw (+/-0.56) to 4.08 W/kg bw (+/-0.48) from time point T1 to T3 which is an increase of +0.38 +/- 0.22 W/kg bw or +11.0% (+/-8.2). The absolute difference in the enhancement of the physical performance between the placebo and the Ubiquinol group of +0.08 W/kg bodyweight was significant (p < 0.03).
CONCLUSIONS:This study demonstrates that daily supplementation of 300 mg Ubiquinol for 6 weeks significantly enhanced physical performance measured as maximum power output by +0.08 W/kg bw (+2.5%) versus placebo in young healthy trained German Olympic athletes. While adherence to a training regimen itself resulted in an improvement in peak power output, as observed by improvement in placebo, the effect of Ubiquinol supplementation significantly enhanced peak power production in comparison to placebo.
- Ubiquinol rescues simvastatin-suppression of mitochondrial content, function and metabolism: Implications for statin-induced rhabdomyolysis. [JOURNAL ARTICLE]
- Eur J Pharmacol 2013 Apr 24.
Statin medications diminish cholesterol biosynthesis and are commonly prescribed to reduce cardiovascular disease. Statins also reduce production of ubiquinol, a vital component of mitochondrial energy production; ubiquinol reduction may contribute to rhabdomyolysis. Human rhabdomyosarcoma cells were treated with either ethanol and dimethyl sulfoxide (DMSO) control, or simvastatin at 5µM or 10µM, or simvastatin at 5µM with ubiquinol at 0.5µM or 1.0µM for 24h or 48h. PGC-1α RNA levels were determined using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Mitochondrial content was determined using flow cytometry and immunocytochemistry. Metabolism was determined by quantification of extracellular acidification rate and oxygen consumption rate. Treatment of human rhabdomyosarcoma cells with simvastatin significantly reduced oxidative, total metabolism, and cellular ATP content in a time- and dose-dependent manner which was rescued by concurrent treatment with ubiquinol. Treatment with simvastatin significantly reduced mitochondrial content as well as cell viability which were both rescued by simultaneous treatment with ubiquinol. This work demonstrates that the addition of ubiquinol to current statin treatment regimens may protect muscle cells from myopathies.
- Concerted expression of the thermogenic and bioenergetic mitochondrial protein machinery in brown adipose tissue. [JOURNAL ARTICLE]
- J Cell Biochem 2013 Apr 20.
Brown adipose tissue (BAT) is specialized in non-shivering thermogenesis through the expression of the mitochondrial uncoupling protein-1 (UCP1). In this paper, we describe the relationship between UCP1 and proteins involved in ATP synthesis. By the use of BATIRKO mice, which have enhanced UCP1 expression in BAT, an increase in ATP synthase as well as in ubiquinol cytochrome c reductase levels was observed. Alterations in mitochondrial mass or variations in ATP levels were not observed in BAT of these mice. In addition, using a protocol of brown adipocyte differentiation, the concerted expression of UCP1 with ATP synthase was found. These two scenarios revealed that increases in the uncoupling machinery of brown adypocites must be concomitantly followed by an enhancement of proteins involved in ATP synthesis. These concerted changes reflect the need to maintain ATP production in an essentially uncoupling cell type. J. Cell. Biochem. © 2013 Wiley Periodicals, Inc.
- Mislocalization of Rieske Protein PetA Predominantly Accounts for the Aerobic Growth Defect of tat Mutants in Shewanella oneidensis. [Journal Article]
- PLoS One 2013; 8(4):e62064.
Shewanella oneidensis exhibits a remarkable versatility in respiration, which largely relies on its various respiratory pathways. Most of these pathways are composed of secretory terminal reductases and multiple associated electron transport proteins that contain cofactors such as Fe-S, molybdopterin, and NiFe. The majority of these cofactors are inserted enzymatically in the cytoplasm, and thus are substrates of the twin-arginine translocation (Tat) protein export system, which transports fully folded proteins. Using genomic array footprinting, we discovered that loss of TatA or TatC caused a reduction in the growth rate of S. oneidensis under aerobic conditions. Mutational analysis of the predicted Tat substrates revealed that PetA, the Rieske Fe-S subunit of the ubiquinol-cytochrome c reductase, predominantly dictates the aerobic growth defect of tat mutants in S. oneidensis. In addition, evidence is presented that the signal sequence in PetA appears to be resistant to cleavage after the protein is inserted into the cytoplasmic membrane.
- RegA, the Regulator of the Two-Component System RegB/RegA of Brucella suis, Is a Controller of Both Oxidative Respiration and Denitrification Required for Chronic Infection in Mice. [Journal Article]
- Infect Immun 2013 Jun; 81(6):2053-61.
Adaptation to oxygen deficiency is essential for virulence and persistence of Brucella inside the host. The flexibility of this bacterium with respect to oxygen depletion is remarkable, since Brucella suis can use an oxygen-dependent transcriptional regulator of the FnrN family, two high-oxygen-affinity terminal oxidases, and a complete denitrification pathway to resist various conditions of oxygen deficiency. Moreover, our previous results suggested that oxidative respiration and denitrification can be simultaneously used by B. suis under microaerobiosis. The requirement of a functional cytochrome bd ubiquinol oxidase for nitrite reductase expression evidenced the linkage of these two pathways, and the central role of the two-component system RegB/RegA in the coordinated control of both respiratory systems was demonstrated. We propose a scheme for global regulation of B. suis respiratory pathways by the transcriptional regulator RegA, which postulates a role for the cytochrome bd ubiquinol oxidase in redox signal transmission to the histidine sensor kinase RegB. More importantly, RegA was found to be essential for B. suis persistence in vivo within oxygen-limited target organs. It is conceivable that RegA acts as a controller of numerous systems involved in the establishment of the persistent state, characteristic of chronic infections by Brucella.
- Cyanide-insensitive quinol oxidase (CIO) from Gluconobacter oxydans is a unique terminal oxidase subfamily of cytochrome bd. [JOURNAL ARTICLE]
- J Biochem 2013 Apr 10.
Cyanide-insensitive terminal quinol oxidase (CIO) is a subfamily of cytochrome bd present in bacterial respiratory chain. We purified CIO from the Gluconobacter oxydans membranes and characterized its properties. The air-oxidized CIO showed some or weak peaks of reduced haemes b and of oxygenated and ferric haeme d, differing from cytochrome bd. CO- and NO-binding difference spectra suggested that haeme d serves as the ligand-binding site of CIO. Notably, the purified CIO showed an extraordinary high ubiquinol-1 oxidase activity with the pH optimum of pH 5-6. The apparent Vmax value of CIO was 17-fold higher than that of G. oxydans cytochrome bo3. In addition, compared with Escherichia coli cytochrome bd, the quinol oxidase activity of CIO was much more resistant to cyanide, but sensitive to azide. The Km value for O2 of CIO was 7- to 10-fold larger than that of G. oxydans cytochrome bo3 or E. coli cytochrome bd. Our results suggest that CIO has unique features attributable to the structure and properties of the O2-binding site, and thus forms a new sub-group distinct from cytochrome bd. Furthermore, CIO of acetic acid bacteria may play some specific role for rapid oxidation of substrates under acidic growth conditions.
- Detecting genome-wide gene transcription profiles associated with high pollution burden in the critically endangered European eel. [Journal Article]
- Aquat Toxicol 2013 May 15.:157-64.
The European eel illustrates an example of a critically endangered fish species strongly affected by human stressors throughout its life cycle, in which pollution is considered to be one of the factors responsible for the decline of the stock. The objective of our study was to better understand the transcriptional response of European eels chronically exposed to pollutants in their natural environment. A total of 42 pre-migrating (silver) female eels from lowly, highly and extremely polluted environments in Belgium and, for comparative purposes, a lowly polluted habitat in Italy were measured for polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs) and brominated flame retardants (BFRs). Multipollutant level of bioaccumulation was linked to their genome-wide gene transcription using an eel-specific array of 14,913 annotated cDNAs. Shared responses to pollutant exposure were observed when comparing the highly polluted site in Belgium with the relatively clean sites in Belgium and Italy. First, an altered pattern of transcription of genes was associated with detoxification, with a novel European eel CYP3A gene and gluthatione S-transferase transcriptionally up-regulated. Second, an altered pattern of transcription of genes associated with the oxidative phosphorylation pathway, with the following genes involved in the generation of ATP being transcriptionally down-regulated in individuals from the highly polluted site: NADH dehydrogenase, succinate dehydrogenase, ubiquinol-cytochrome c reductase, cytochrome c oxidase and ATP synthase. Although we did not measure metabolism directly, seeing that the transcription level of many genes encoding enzymes involved in the mitochondrial respiratory chain and oxidative phosphorylation were down-regulated in the highly polluted site suggests that pollutants may have a significant effect on energy metabolism in these fish.
- AtWRKY40 and AtWRKY63 Modulate the Expression of Stress-Responsive Nuclear Genes Encoding Mitochondrial and Chloroplast Proteins. [Journal Article]
- Plant Physiol 2013 May; 162(1):254-71.
The expression of a variety of nuclear genes encoding mitochondrial proteins is known to adapt to changes in environmental conditions and retrograde signaling. The presence of putative WRKY transcription factor binding sites (W-boxes) in the promoters of many of these genes prompted a screen of 72 annotated WRKY factors in the Arabidopsis (Arabidopsis thaliana) genome for regulators of transcripts encoding mitochondrial proteins. A large-scale yeast one-hybrid screen was used to identify WRKY factors that bind the promoters of marker genes (Alternative oxidase1a, NADH dehydrogenaseB2, and the AAA ATPase Ubiquinol-cytochrome c reductase synthesis1), and interactions were confirmed using electromobility shift assays. Transgenic overexpression and knockout lines for 12 binding WRKY factors were generated and tested for altered expression of the marker genes during normal and stress conditions. AtWRKY40 was found to be a repressor of antimycin A-induced mitochondrial retrograde expression and high-light-induced signaling, while AtWRKY63 was identified as an activator. Genome-wide expression analysis following high-light stress in transgenic lines with perturbed AtWRKY40 and AtWRKY63 function revealed that these factors are involved in regulating stress-responsive genes encoding mitochondrial and chloroplast proteins but have little effect on more constitutively expressed genes encoding organellar proteins. Furthermore, it appears that AtWRKY40 and AtWRKY63 are particularly involved in regulating the expression of genes responding commonly to both mitochondrial and chloroplast dysfunction but not of genes responding to either mitochondrial or chloroplast perturbation. In conclusion, this study establishes the role of WRKY transcription factors in the coordination of stress-responsive genes encoding mitochondrial and chloroplast proteins.