Mitochondria-targeted molecules comprising the lipophilic TPP (triphenylphosphonium) cation covalently linked to a hydrophobic bioactive moiety are used to modify and probe mitochondria in cells and in vivo. However, it is unclear how hydrophobicity affects the rate and extent of their uptake into mitochondria within cells, making it difficult to interpret experiments because their intracellula...

Protein domain movement of the Rieske iron-sulfur protein has been speculated to play an essential role in the bifurcated oxidation of ubiquinol catalyzed by the cytochrome bc1 complex. To better understand the electron transfer mechanism of the bifurcated ubiquinol oxidation at Qp site, we fixed the head domain of ISP at the cyt c1 position by creating an intersubunit disulfide bond between tw...

During the electron transfer through the cytochrome bc(1) complex (ubiquinol-cytochrome c oxidoreductase or complex III), protons are translocated across the membrane, and production of superoxide anion radicals (O(2)(*-)) is observed. The bc(1) complex is purified from broken mitochondrial preparation prepared from frozen heart muscles by repeated detergent solubilization and salt fractionatio...

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 ox...

Expression of the genes of the alkane degradation pathway encoded in the Pseudomonas putida OCT plasmid are subject to negative and dominant global control depending on the carbon source used and on the physiological status of the cell. We investigated the signals responsible for this control in chemostat cultures under conditions of nutrient or oxygen limitation. Our results show that this glo...

by ISAAC PAUL FORQUER Washington State University December 2008 Chair: David M. Kramer The oxidation of ubiquinol by the cytochrome bc1 complex is usually a tightly controlled process, however there are instances when the reaction is compromised by mutation or other external factors such as inhibitors that leads to superoxide production. The first part of this dissertation compares the electron...

In mitochondria, four respiratory-chain complexes drive oxidative phosphorylation by sustaining a proton-motive force across the inner membrane that is used to synthesize ATP. The question of how the densely packed proteins of the inner membrane are organized to optimize structure and function has returned to prominence with the characterization of respiratory-chain supercomplexes. Supercomplex...

Ilicicolin H is an antibiotic isolated from the "imperfect" fungus Cylindrocladium iliciola strain MFC-870. Ilicicolin inhibits mitochondrial respiration by inhibiting the cytochrome bc(1) complex. In order to identify the site of ilicicolin action within the bc(1) complex we have characterized the effects of ilicicolin on the cytochrome bc(1) complex of Saccharomyces cerevisiae. Ilicicolin inh...

Evidence on the efficacy of high-dose coenzyme Q10 (CoQ10) in Parkinson's disease (PD) is conflicting. An open-label dose-escalation study was performed to examine the effects of CoQ10 on biomarkers of oxidative damage and clinical outcomes in 16 subjects with early idiopathic PD. Each dose (400, 800, 1200, and 2400 mg/day) was consumed daily for 2 weeks. High-dose CoQ10 was well tolerated and ...

A tissue-specific distribution of the various vitamin E forms, tocotrienols and tocopherols, has been found, suggesting that these forms have unique roles in cellular functions. A sensitive procedure is described for the simultaneous determination of individual tocopherols, tocotrienols, ubiquinols, and ubiquinones using gradient high pressure liquid chromatography (HPLC) and electrochemical de...