Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.9.3.1 (cytochrome oxidase)
 8,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The amino- and carboxy-terminal domains of mitochondrially encoded cytochrome c oxidase subunit II (Cox2p) are translocated out of the matrix to the intermembrane space. We have carried out a genetic screen to identify components required to export the biosynthetic enzyme Arg8p, tethered to the Cox2p C terminus by a translational gene fusion inserted into mtDNA. We obtained multiple alleles of COX18, PNT1, and MSS2, as well as mutations in CBP1 and PET309. Focusing on Cox18p, we found that its activity is required to export the C-tail of Cox2p bearing a short C-terminal epitope tag. This is not a consequence of reduced membrane potential due to loss of cytochrome oxidase activity because Cox2p C-tail export was not blocked in mitochondria lacking Cox4p. Cox18p is not required to export the Cox2p N-tail, indicating that these two domains of Cox2p are translocated by genetically distinct mechanisms. Cox18p is a mitochondrial integral inner membrane protein. The inner membrane proteins Mss2p and Pnt1p both coimmunoprecipitate with Cox18p, suggesting that they work together in translocation of Cox2p domains, an inference supported by functional interactions among the three genes.
 ...
PMID:Cox18p is required for export of the mitochondrially encoded Saccharomyces cerevisiae Cox2p C-tail and interacts with Pnt1p and Mss2p in the inner membrane. 1195 Sep 26

A global depletion of cellular copper as the result of a deficiency in high-affinity copper uptake was previously shown to affect the phenotype and life span of the filamentous fungus Podospora anserina. We report here the construction of a strain in which the delivery of copper to complex IV of the mitochondrial respiratory chain is affected. This strain, PaCox17::ble, is a PaCox17-null mutant that does not synthesize the molecular chaperone targeting copper to cytochrome c oxidase subunit II. PaCox17::ble is characterized by a decreased growth rate, a reduction in aerial hyphae formation, reduced female fertility, and a dramatic increase in life span. The mutant respires via a cyanide-resistant alternative pathway, displays superoxide dismutase (SOD) activity profiles significantly differing from those of the wild-type strain and is characterized by a stabilization of the mitochondrial DNA. Collectively, the presented data define individual components of a molecular network effective in life span modulation and copper as an element with a dual effect. As a cofactor of complex IV of the respiratory chain, it is indirectly involved in the generation of reactive oxygen species (ROS) and thereby plays a life span-limiting role. In contrast, Cu/Zn SOD as a ROS-scavenging enzyme lowers molecular damage and thus positively affects life span. Such considerations explain the reported differences in life span of independent mutants and spread more light on the delicate tuning of the molecular network influencing biological ageing.
 ...
PMID:Impact of a disruption of a pathway delivering copper to mitochondria on Podospora anserina metabolism and life span. 1487 50

The objectives of this study were to determine the effects of low or high feed efficiency (FE) on a) protein oxidation, b) the activities of various respiratory chain complexes, and c) expression of various mitochondrial proteins in male broilers within a single genetic line. Tissue homogenate or mitochondria were isolated from breast muscle of broilers with high (0.80 +/- 0.01) and low FE (0.62 +/- 0.02). The complex activities were measured spectrophotometrically, and the levels of oxidized protein (carbonyl) and immunoreactive mitochondrial proteins were analyzed using Western blots. Protein carbonyl levels were higher in low FE compared with high FE broilers breast muscle, which indicated enhanced protein oxidation in low FE mitochondria. Activities of all respiratory chain complexes (I, II, III, IV) were higher in high FE compared with low FE broilers for breast mitochondria. Whereas the expression of immunoreactive proteins was higher in low FE muscle mitochondria for 5 mitochondrial proteins [core I, cyt c1, cyt b (complex III), COX II (cytochrome c oxidase subunit II, complex IV), and adenine nucleotide translocator (ANT1)], there were no differences between groups in the expression of 9 other respiratory chain protein subunits associated with complexex I, II, III, IV, and V. SDS-PAGE revealed a protein band of 47 kDa that was expressed at a higher level in low FE compared with high FE mitochondria. The differential expression of certain mitochondrial proteins and the 47-kDa band might be a compensatory response either to the lower complex activities or increased protein oxidation observed in low FE birds.
 ...
PMID:Low feed efficient broilers within a single genetic line exhibit higher oxidative stress and protein expression in breast muscle with lower mitochondrial complex activity. 1504 2

The membrane assembly of the respiratory complexes requires the membrane insertases Oxa1 in mitochondria and YidC in bacteria. Oxa1 is responsible for the insertion of the mitochondrial cytochrome c oxidase subunit II (CoxII). Here, we investigated whether YidC, the bacterial Oxa1 homolog, plays a crucial role in the assembly of the bacterial subunit II (CyoA) of cytochrome bo oxidase. CyoA spans the membrane twice and is made with a cleavable signal peptide. We find that translocation of the short N-terminal domain of CyoA is YidC-dependent. In contrast, both the SecA/SecYEG complex and YidC are required for translocation of the large C-terminal domain. By studying the N-terminal domain of CyoA alone, we find that translocation is unaffected when SecE is depleted, suggesting that the YidC insertase on its own catalyzes membrane insertion of the N-terminal region of CyoA. Strikingly, we find that the translocation of the N-terminal domain is a prerequisite for translocation of the C-terminal domain in the full-length CyoA protein because translocation of the large C-terminal domain alone in a truncated CyoA derivative was observed in the absence of YidC. This work shows that the distinct domains of CyoA have different translocation requirements (YidC only and Sec/YidC) and confirms that the membrane biogenesis of subunit II of cytochrome oxidase in bacteria and mitochondria have conserved features.
 ...
PMID:Membrane biogenesis of subunit II of cytochrome bo oxidase: contrasting requirements for insertion of N-terminal and C-terminal domains. 1648 30

Recent studies have suggested that mutations in the mitochondrial genome (mtDNA) may play a role in the development and response to treatment for human cancer. The aim of this study was to investigate whether mtDNA variations have any prognostic relevance, to clarify the spectra of mtDNA variation and to determine whether there was any correlation to known prognostic factors in acute myeloid leukemia (AML). To elucidate this, we sequenced the entire mtDNA in 56 AML patients and 14 control subjects. When analyzing the biologic impact of the non-synonymous variations in the mtDNA coding genes, we found an inferior disease-free survival for patients exhibiting variations in the two most important catalytic genes of the complex IV of the oxidative phosphorylation complexes (OXPHOS), that is, the cytochrome c oxidase subunit I and the cytochrome c oxidase subunit II (hazard ratio 2.6, P = 0.03; multivariate analysis). In addition, the most frequent variation was the T16311C in the control region, which was found in 11 (20%) of the 56 patients. This observation was confirmed in another cohort of 173 diagnostic AML samples. In this expanded group, the T16311C variation tended to be associated with chromosomal abnormalities.
 ...
PMID:Characterization and prognostic significance of mitochondrial DNA variations in acute myeloid leukemia. 2344 69

Metallothioneins (MT) are involved in a broad range of cellular processes and play a major role in protection of cells towards various stressors. Two functions of MTs, namely the maintaining of the homeostasis of transition metal ions and the redox balance, are directly linked to the functioning of mitochondria. Dyshomeostasis of MTs is often related with malfunctioning of mitochondria; however, the mechanism by which MTs affect the mitochondrial respiratory chain is still unknown. We demonstrated that overexpression of MT-2A in HEK cell line decreased the oxidative phosphorylation capacity of the cells. HEK cells overexpressing MT-2A demonstrated reduced oxygen consumption and lower cellular ATP levels. MT-2A did not affect the number of mitochondria, but reduced specifically the level of cytochrome c oxidase subunit II protein, which resulted in lower activity of the complex IV.
...
PMID:Metallothionein 2A affects the cell respiration by suppressing the expression of mitochondrial protein cytochrome c oxidase subunit II. 2580 18