Human CIA30 is involved in the early assembly of mitochondrial complex I and mutations in its gene cause disease.
AuthorsDunning CJ, McKenzie M, Sugiana C, Lazarou M, Silke J, Connelly A, Fletcher JM, Kirby DM, Thorburn DR, Ryan MT
JournalEMBO J
PubMed ID17557076
'In humans, complex I of the respiratory chain is composed of seven mitochondrial DNA (mtDNA)-encoded and 38 nuclear-encoded subunits that assemble together in a process that is poorly defined. To date, only two complex I assembly factors have been identified and how each functions is not clear. Here, we show ... More
Cytochrome c oxidase-deficient patients have distinct subunit assembly profiles.
AuthorsHanson BJ, Carrozzo R, Piemonte F, Tessa A, Robinson BH, Capaldi RA
JournalJ Biol Chem
PubMed ID11278850
'Cytochrome c oxidase (COX) deficiency is the most common respiratory chain defect in childhood and is clinically heterogeneous. We report a study of six patients with COX deficiencies. Two of the patients had as yet undefined defects, three patients had Surf-1 mutations, and one patient had a 15-base pair deletion ... More
Yeast Sco1, a protein essential for cytochrome c oxidase function is a Cu(I)-binding protein.
AuthorsNittis T, George GN, Winge DR
JournalJ Biol Chem
PubMed ID11546815
'Sco1 is a conserved essential protein, which has been implicated in the delivery of copper to cytochrome c oxidase, the last enzyme of the electron transport chain. In this study, we show for the first time that the purified C-terminal domain of yeast Sco1 binds one Cu(I)/monomer. X-ray absorption spectroscopy ... More
Functional constraints of nuclear-mitochondrial DNA interactions in xenomitochondrial rodent cell lines.
AuthorsDey R, Barrientos A, Moraes CT
JournalJ Biol Chem
PubMed ID10908562
'The co-evolution of nuclear and mitochondrial genomes in vertebrates led to more than 100 specific interactions that are crucial for an optimized ATP generation. These interactions have been examined by introducing rat mtDNA into mouse cells devoid of mitochondrial DNA (mtDNA). When mtDNA-less cells derived from the common mouse (Mus ... More
Chronic exposure to nitric oxide alters the free iron pool in endothelial cells: role of mitochondrial respiratory complexes and heat shock proteins.
AuthorsRamachandran A, Ceaser E, Darley-Usmar VM
JournalProc Natl Acad Sci U S A
PubMed ID14691259
'The mechanisms of nitric oxide (NO) signaling include binding to the iron centers in soluble guanylate cyclase and cytochrome c oxidase and posttranslational modification of proteins by S-nitrosation. Low levels of NO control mitochondrial number in cells, but little is known of the impact of chronic exposure to high levels ... More
Mouse CLK-1 is imported into mitochondria by an unusual process that requires a leader sequence but no membrane potential.
AuthorsJiang N, Levavasseur F, McCright B, Shoubridge EA, Hekimi S
JournalJ Biol Chem
PubMed ID11387338
'clk-1 has been identified and characterized in the nematode Caenorhabditis elegans as a gene that affects the rates, regularity, and synchrony of physiological processes. The CLK-1 protein is mitochondrial and is required for ubiquinone biosynthesis in yeast and in worms, but its biochemical function remains unclear. We have studied the ... More
Human complex I defects can be resolved by monoclonal antibody analysis into distinct subunit assembly patterns.
AuthorsTriepels RH, Hanson BJ, van den Heuvel LP, Sundell L, Marusich MF, Smeitink JA, Capaldi RA
JournalJ Biol Chem
PubMed ID11112787
Complex I defects are one of the most frequent causes of mitochondrial respiratory chain disorders. Therefore, it is important to find new approaches for detecting and characterizing Complex I deficiencies. In this paper, we introduce a new set of monoclonal antibodies that react with 39-, 30-, 20-, 18-, 15-, and ... More
Expression of mtDNA and nDNA encoded respiratory chain proteins in chemically and genetically-derived Rho0 human fibroblasts: a comparison of subunit proteins in normal fibroblasts treated with ethidium bromide and fibroblasts from a patient with mtDNA depletion syndrome.
AuthorsMarusich MF, Robinson BH, Taanman JW, Kim SJ, Schillace R, Smith JL, Capaldi RA
JournalBiochim Biophys Acta
PubMed ID9540845
Although much progress has been made in identifying genetic defects associated with mitochondrial diseases, the protein expression patterns of most disorders are poorly understood. Here we use immunochemical techniques to describe subunit expression patterns of respiratory chain enzyme complexes II (succinate dehydrogenase: SD) and IV (cytochrome c oxidase: COX) in ... More
Simultaneous trichromatic fluorescence detection of proteins on Western blots using an amine-reactive dye in combination with alkaline phosphatase- and horseradish peroxidase-antibody conjugates.
AuthorsMartin K, Hart C, Liu J, Leung WY, Patton WF
JournalProteomics
PubMed ID12872222
Three-color fluorescence detection methods are described based upon covalently coupling the dye 2-methoxy-2,4-diphenyl-2(2H)-furanone (MDPF) to proteins immobilized on poly(vinylidene difluoride) (PVDF) membranes, followed by detection of target proteins using alkaline-phosphatase-conjugated reporter molecules in combination with the fluorogenic substrate 9H-(1,3-dichloro-9,9-dimethylacridin-2-one-7-yl) phosphate (DDAO-phosphate) as well as horseradish peroxidase-conjugated reporter molecules in combination ... More
Mitochondrial respiration and ATP production are significantly impaired in striatal cells expressing mutant huntingtin.
AuthorsMilakovic T, Johnson GV
JournalJ Biol Chem
PubMed ID15983033
There is significant evidence that energy production impairment and mitochondrial dysfunction play a role in the pathogenesis of Huntington disease. Nonetheless, the specific mitochondrial defects due to the presence of mutant huntingtin have not been fully elucidated. To determine the effects of mutant huntingtin on mitochondrial energy production, a thorough ... More