Ccme-The cytochrome pathway and cytochrome C biogenesis
Ontology highlight
ABSTRACT:
ORGANISM(S): Arabidopsis thaliana
PROVIDER: GSE7995 | GEO | 2007/06/20
SECONDARY ACCESSION(S): PRJNA100777
REPOSITORIES: GEO
Similar Datasets
Project description:The homozygous arabidopsis line 9S9 overproducing AtCCME-HIS (At3g1790), a mitochondrial heme chaperon involved in c-type cytochrome maturation will be compared with the corresponding wild type (Wassilievskjia).
2006-08-23 | E-MEXP-779 | biostudies-arrayexpress
Project description:rs04-01_cytc - antimycine a - Is there a retrograde regulation of mitochondrial cytochrome pathway ? - Presence of an inhibitor of the cytochrome pathway (antimycine A). This treatment induces the expression of a gene coding for an alternative oxydase (AOX1a) and one of the two genes coding for apocytochrome c (CYTc-a). Keywords: treated vs untreated comparison
2007-06-20 | GSE7994 | GEO
Project description:Defects in mitochondrial oxidative phosphorylation complexes, altered bioenergetics and metabolic shift are often seen in cancers. Here we show a role for the dysfunction of electron transport chain component, cytochrome c oxidase (CcO) in cancer progression. We show that genetic silencing of the CcO complex by shRNA expression and loss of CcO activity in multiple cell types from the mouse and human sources resulted in metabolic shift to glycolysis, loss of anchorage dependent growth and acquired invasive phenotypes. Disruption of CcO complex caused loss of transmembrane potential and induction of Ca2+/Calcineurin-mediated retrograde signaling. Propagation of this signaling, includes activation of PI3-kinase, IGF1R and Akt, Ca2+ sensitive transcription factors and also, TGF1, MMP16, periostin that are involved in oncogenic progression. Whole genome expression analysis showed up regulation of genes involved in cell signaling, extracellular matrix interactions, cell morphogenesis, cell motility and migration. The transcription profiles reveal extensive similarity to retrograde signaling initiated by partial mtDNA depletion, though distinct differences are observed in signaling induced by CcO dysfunction. The possible CcO dysfunction as a biomarker for cancer progression was supported by data showing that esophageal tumors from human patients show reduced CcO subunits IVi1 and Vb in regions that were previously shown to be hypoxic core of the tumors. Our results show that mitochondrial electron transport chain defect initiates a retrograde signaling. These results suggest that a defect in CcO complex can potentially induce tumor progression. Total RNA from control and CcO IVi1 silenced cells was extract. Three independent samples were generated for control and silenced, respectively.
2015-05-05 | E-GEOD-68525 | biostudies-arrayexpress
Project description:Defects in mitochondrial oxidative phosphorylation complexes, altered bioenergetics and metabolic shift are often seen in cancers. Here we show a role for the dysfunction of electron transport chain component, cytochrome c oxidase (CcO) in cancer progression. We show that genetic silencing of the CcO complex by shRNA expression and loss of CcO activity in multiple cell types from the mouse and human sources resulted in metabolic shift to glycolysis, loss of anchorage dependent growth and acquired invasive phenotypes. Disruption of CcO complex caused loss of transmembrane potential and induction of Ca2+/Calcineurin-mediated retrograde signaling. Propagation of this signaling, includes activation of PI3-kinase, IGF1R and Akt, Ca2+ sensitive transcription factors and also, TGF1, MMP16, periostin that are involved in oncogenic progression. Whole genome expression analysis showed up regulation of genes involved in cell signaling, extracellular matrix interactions, cell morphogenesis, cell motility and migration. The transcription profiles reveal extensive similarity to retrograde signaling initiated by partial mtDNA depletion, though distinct differences are observed in signaling induced by CcO dysfunction. The possible CcO dysfunction as a biomarker for cancer progression was supported by data showing that esophageal tumors from human patients show reduced CcO subunits IVi1 and Vb in regions that were previously shown to be hypoxic core of the tumors. Our results show that mitochondrial electron transport chain defect initiates a retrograde signaling. These results suggest that a defect in CcO complex can potentially induce tumor progression.
2015-05-05 | GSE68525 | GEO
Project description:We describe a role for the poorly annotated protein PGRMC2 in retrograde transport of heme from mitochondria to the nucleus. In absence of PGRMC2, less signaling heme reaches the nucleus, with a consequent alteration of heme-sensitive transcriptional programs that ultimately engenders severe mitochondrial dysfunction in brown adipocytes. These mitochondrial defects compromise, not only the primary function of BAT, to activate thermogenesis and preserve body temperature, but also its contribution to maintain systemic glucose and lipid homeostasis.
2019-09-01 | GSE124621 | GEO
Project description:Mitochondrial cytochrome c oxidase (CcO) or respiratory chain complex IV is a heme aa3-copper oxygen reductase containing metal centers essential for holo-complex biogenesis and enzymatic function that are assembled by subunit-specific metallochaperones. The enzyme has two copper sites located in the catalytic core subunits. The COX1 subunit harbors the CuB site that tightly associates with heme a3 while the COX2 subunit contains the binuclear CuA site. Here, we report that in human cells the CcO copper chaperones form macromolecular assemblies and cooperate with several twin CX9C proteins to control heme a biosynthesis and coordinate copper transfer sequentially to the CuA and CuB sites. These data on CcO illustrate a mechanism that regulates the biogenesis of macromolecular enzymatic assemblies with several catalytic metal redox centers and prevents the accumulation of cytotoxic reactive assembly intermediates We characterized the proteome of COX11, COX19 and PET191 by AP + LC-MS-MS
2022-08-12 | PXD034577 | Pride
Project description:Mitochondrial cytochrome c oxidase (CcO) or respiratory chain complex IV is a heme aa3-copper oxygen reductase containing metal centers essential for holo-complex biogenesis and enzymatic function that are assembled by subunit-specific metallochaperones. The enzyme has two copper sites located in the catalytic core subunits. The COX1 subunit harbors the CuB site that tightly associates with heme a3 while the COX2 subunit contains the binuclear CuA site. Here, we report that in human cells the CcO copper chaperones form macromolecular assemblies and cooperate with several twin CX9C proteins to control heme a biosynthesis and coordinate copper transfer sequentially to the CuA and CuB sites. These data on CcO illustrate a mechanism that regulates the biogenesis of macromolecular enzymatic assemblies with several catalytic metal redox centers and prevents the accumulation of cytotoxic reactive assembly intermediates. We characterized the proteome of COX11, COX19 and PET191 by AP + LC-MS-MS
2022-08-12 | PXD034579 | Pride
Project description:Mitochondrial cytochrome c oxidase (CcO) or respiratory chain complex IV is a heme aa3-copper oxygen reductase containing metal centers essential for holo-complex biogenesis and enzymatic function that are assembled by subunit-specific metallochaperones. The enzyme has two copper sites located in the catalytic core subunits. The COX1 subunit harbors the CuB site that tightly associates with heme a3 while the COX2 subunit contains the binuclear CuA site. Here, we report that in human cells the CcO copper chaperones form macromolecular assemblies and cooperate with several twin CX9C proteins to control heme a biosynthesis and coordinate copper transfer sequentially to the CuA and CuB sites. These data on CcO illustrate a mechanism that regulates the biogenesis of macromolecular enzymatic assemblies with several catalytic metal redox centers and prevents the accumulation of cytotoxic reactive assembly intermediates. We characterized the proteome of COX11, COX19 and PET191 by AP + LC-MS-MS
2022-08-12 | PXD034578 | Pride
Project description:Mitochondrial cytochrome c oxidase (CcO) or respiratory chain complex IV is a heme aa3-copper oxygen reductase containing metal centers essential for holo-complex biogenesis and enzymatic function that are assembled by subunit-specific metallochaperones. The enzyme has two copper sites located in the catalytic core subunits. The COX1 subunit harbors the CuB site that tightly associates with heme a3 while the COX2 subunit contains the binuclear CuA site. Here, we report that in human cells the CcO copper chaperones form macromolecular assemblies and cooperate with several twin CX9C proteins to control heme a biosynthesis and coordinate copper transfer sequentially to the CuA and CuB sites. These data on CcO illustrate a mechanism that regulates the biogenesis of macromolecular enzymatic assemblies with several catalytic metal redox centers and prevents the accumulation of cytotoxic reactive assembly intermediates. We characterized the proteome of COX11, COX19 and PET191 by AP + LC-MS-MS
2022-08-12 | PXD034576 | Pride
Project description:Cytochrome P450 enzymes (P450s) are a superfamily of monooxygenases that utilise a cysteine thiolate ligated heme moiety to perform a wide range of demanding oxidative transformations. Given the oxidative power of active intermediate formed within P450s during their active cycle, it is remarkable that these enzymes can avoid self-oxidation as well as retaining the axial cysteine ligand in the deprotonated – and thus highly acidic – thiolate form. Whilst little is known about the process of heme incorporation during P450 folding, there is an overwhelming preference for one heme orientation within the P450 active site. Indeed, very few structures to date contain an alternate heme orientation, of which two are OxyA homologues from glycopeptide antibiotic (GPA) biosynthesis. Given the apparent preference for the unusual heme orientation shown by OxyA enzymes, we investigated the OxyA homologue from kistamicin biosynthesis, which is an atypical GPA. We determined that OxyAkis is highly sensitive to oxidative damage by peroxide, with both UV an EPR measurements shows a rapid bleaching of the heme signal. We determined the structure of OxyAkis and found a mixed population of heme orientations present in this enzyme. Analysis further revealed that an unprecedented oxidative modification of the heme was detected, which that correlated with the presence of the alternate heme orientation in the protein. These results provide evidence that the typical heme orientation in Cytochrome P450s can help to prevent potential autocatalytic modification of the heme – and hence deactivation of the enzyme – during P450 catalysis. It also suggests that some P450 enzymes involved in GPA biosynthesis may be especially prone to oxidative damage due to the heme orientation found in their active sites.
2022-05-20 | PXD030867 | Pride