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
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
Dysfunctions of cellular oxidative metabolism in patients with mutations in the NDUFS1 and NDUFS4 genes of complex I.
AuthorsIuso A, Scacco S, Piccoli C, Bellomo F, Petruzzella V, Trentadue R, Minuto M, Ripoli M, Capitanio N, Zeviani M, Papa S
JournalJ Biol Chem
PubMed ID16478720
The pathogenic mechanism of a G44A nonsense mutation in the NDUFS4 gene and a C1564A mutation in the NDUFS1 gene of respiratory chain complex I was investigated in fibroblasts from human patients. As previously observed the NDUFS4 mutation prevented complete assembly of the complex and caused full suppression of 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
Loss of Aif function causes cell death in the mouse embryo, but the temporal progression of patterning is normal.
AuthorsBrown D, Yu BD, Joza N, Bénit P, Meneses J, Firpo M, Rustin P, Penninger JM, Martin GR
JournalProc Natl Acad Sci U S A
PubMed ID16788063
Apoptosis-inducing factor (AIF) is an evolutionarily conserved, ubiquitously expressed flavoprotein with NADH oxidase activity that is normally confined to mitochondria. In mammalian cells, AIF is released from mitochondria in response to apoptotic stimuli and translocates to the nucleus where it is thought to bind DNA and contribute to chromatinolysis and ... More
Apoptosis induction by activator protein 2alpha involves transcriptional repression of Bcl-2.
AuthorsWajapeyee N, Britto R, Ravishankar HM, Somasundaram K
JournalJ Biol Chem
PubMed ID16533807
Activator protein 2alpha (AP-2alpha) induces cytotoxicity by inducing cell cycle arrest and apoptosis. In this study we investigated the mechanism of apoptosis induction by AP-2alpha. We found that AP-2alpha induced apoptosis efficiently in cells treated with benzyloxycar-bonyl-IETD-fluoromethyl ketone or FADD-silenced cells but failed to do so in benzyloxycarbonyl-LEHD-fluoromethyl ketone-treated or ... More
Hypothyroid phenotype is contributed by mitochondrial complex I inactivation due to translocated neuronal nitric-oxide synthase.
Although transcriptional effects of thyroid hormones have substantial influence on oxidative metabolism, how thyroid sets basal metabolic rate remains obscure. Compartmental localization of nitric-oxide synthases is important for nitric oxide signaling. We therefore examined liver neuronal nitric-oxide synthase-alpha (nNOS) subcellular distribution as a putative mechanism for thyroid effects on rat ... More