Disease relevance of mt-Cytb

• Experiments on O2 consumption and cytochrome b oxidation-reduction changes in ascites cells showed only the first two of these effects in the intact tumor cells [1].
• This cytochrome b is reducible by hypoxia, but not by cyanide, indicating that it does not participate in the energy production by the respiratory chain [2].
• These results identify cytochrome b as the locus of regulation of electron transport in BAT mitochondria under conditions of heat stress [3].
• We have examined the relationship between the expression of hepcidin in the liver and the expression of the iron-transport molecules divalent-metal transporter 1, duodenal cytochrome b, hephaestin and Ireg1 in the duodenum of rats switched from an iron-replete to an iron-deficient diet or treated to induce an acute phase response [4].
• Both mature and incompletely processed cytochrome b mRNA levels were depressed after 45 min of ischemia and 15 min of reflow; levels rebounded to above normal after 2 h of reflow and then declined over the next 22 h [5].

High impact information on mt-Cytb

• Atovaquone was shown to inhibit the respiratory chain of T. gondii and mammalian mitochondria between cytochrome b and c1 as occurs with antimycin A1 [6].
• Loss of mRNAs generating ATP was highly selective since mRNAs for other energy production enzymes, (cytochrome c, cytochrome b, and malate dehydrogenase), and genes important in glycolysis (pyruvate kinase and glyceraldehyde-3-phosphate dehydrogenase) were unaffected even at 24 and 48 h [7].
• After 2 weeks of HCCL treatment, hepatic contents of the mature mitochondrial mRNAs (expressed normalized to 28 S rRNA) encoding subunit II of cytochrome c oxidase (CO II), subunit 1 of NADH dehydrogenase (ND1), and cytochrome b were reduced to values 40-60% of those observed in RNA from control liver tissue [8].
• To investigate the degree of specificity of the localization of cytochrome b5 isoforms, we studied their subcellular distributions with antipeptide antibodies, one specific for microsomal cytochrome b5, one specific for outer membrane cytochrome b, and one against a sequence common to the two cytochromes [9].
• We then analyzed biochemically characterized rat liver subcellular fractions by Western blotting and found that outer mitochondrial membrane cytochrome b was not present on endoplasmic reticulum membranes [9].

Biological context of mt-Cytb

• The amino acid and nucleotide sequences of the cytochrome b genes of mammals and yeast [Nobrega and Tzagoloff, J. Biol. Chem. 255 (1980) 9828] were compared to reveal structural differences in two very different species [10].
• We sequenced the cytochrome b gene from the species used to identify potential amino acid substitutions involved in such interactions [11].
• Three of them were synonymous mutations, one was a missense mutation in cytochrome b gene (A-->G at nt 15422), and the last one was the 15915 mutation in tRNA(Thr) gene [12].
• We analyzed the phylogenetic relationships of echimyid genera based on sequences of the cytochrome b, 12S, and 16S mitochondrial genes [13].
• Molecular phylogeny of European muroid rodents based on complete cytochrome b sequences [14].

Anatomical context of mt-Cytb

• Liver mitochondria from HCCL-treated rats also demonstrate decreased cytochrome content per mg of mitochondrial protein (25% decrease of cytochrome b and 52% decrease of cytochrome a + a3 as compared with control rats) [15].
• Consistent with these result was the observation that with liver mitochondrial the magnitude of the cytochrome b oxidation-reduction shift was greater for Ca2+ than for ADP, whereas calcium responses never surpassed the ADP response in heart mitochondria [16].
• Peritoneal macrophages were elicited in rats by using casein as a stimulus; when stimulated with phorbol 12-myristate 13-acetate (PMA) they produced O2.-. Nearly 60% of the total cytochrome b had a low Em,7.0 of -247 mV, typical of the cytochrome b component found in the NADPH-dependent O2(.-)-generating oxidase of neutrophils [17].
• In previous studies, MPP+ provoked oxidation of cytochrome b and K+ leakage into the extracellular space of rat striatal slices [18].
• The rate of O2.- generation by macrophages was 1.23 mol of O2.-/s per mol of cytochrome b [17].

Associations of mt-Cytb with chemical compounds

• A third pathway utilizes both ubiquinone and cytochrome b and is partiayly inhibited by either thenoyltrifluoroacetone or antimycin A [19].
• Thenoyltrifluoroacetone completely inhibits fumarate synthesis and reduction of cytochrome b by succinate [19].
• The substrate-dependent pattern of tBOOH-induced NAD(P)H (NADH plus NADPH) and cytochrome b oxidation was similar to that seen for respiratory inhibition and Ca2+ efflux suggesting that NAD(P)H may be a common factor in both responses [20].
• The level of cytochrome b mRNA increased at 28 mM glucose compared with islets cultured at 11 mM glucose (140 +/- 14%) [21].
• Formation of orotate is only partially inhibited by thenolytrifluoroacetone and the inhibitor does not prevent reduction of cytochrome b by dihydroorotate [19].

Physical interactions of mt-Cytb

• We propose that the antiapoptotic properties of Bcl-2 are related to the reduction of mitochondrial complex I activity and lowered mitochondrial cytochrome b and c levels [22].

Other interactions of mt-Cytb

• Immunoadsorption studies using antibody-coated polyacrylamide beads showed that significant OM cytochrome b-mediated activity is present in the microsomal membrane, and that cytochrome b5-mediated activity also exists in the mitochondrial outer membrane [23].
• Dihydroorotate dehydrogenase differs from succinate dehydrogenase both in its utilization of ubiquinone and in the mechanism of cytochrome b reduction [19].
• The lower islet mtDNA contents were paralleled by a decreased content of islet mtRNA (12S ribosomal RNA and cytochrome b messenger RNA) [24].
• Genes encoding the apical iron transport-related proteins [divalent metal transporter 1 (DMT1) and duodenal cytochrome b] were strongly induced at all ages studied, whereas increases in mRNA encoding the basolateral proteins iron-regulated gene 1 and hephaestin were observed only by real-time PCR [25].
• Using functional and spectrophotometric measurements in an inducible PC12-Tet-on-bcl-2 cell line we demonstrate that induction of Bcl-2 overexpression rapidly reduced cytochrome b and c levels as well as complex I activity [22].

Analytical, diagnostic and therapeutic context of mt-Cytb

• Cellular mRNA levels for the mitochondrial DNA-encoded cytochrome b and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were determined by Northern-blot analysis [21].
• Male rat liver mitochondria were isolated by centrifugation; oxygen uptake, reduced forms of cytochrome b, c + c1, a + a3, and flavoprotein, intramitochondrial concentrations of acetyl coA, acid-soluble coA, acid-insoluble coA, and ATP content were measured after incubation with and without MO [26].
• The rat carotid body is able to generate H2O2 in type-I cells with the aid of an electron-transferring chain with cytochrome b as the major component as it can be detected by spectrophotometry as well as confocal laser-microscopy [2].
• To relate metabolic effects of MPP+ with tissue electrophysiology, extracellular potassium ion activity [K+]o was measured by microelectrodes simultaneous to optical monitoring of reduction/oxidation (redox) activity of cytochrome b during superfusion of MPP+ onto rat striatal and hippocampal slices [27].
• Contents of NRF-1 mRNA and MRP-RNase RNA increased to maximum or sub-maximum level 1 h after hepatectomy. mtDNA and cytochrome b mRNA increased to maximum level 3 h after [28].

References