The Experts below are selected from a list of 327 Experts worldwide ranked by ideXlab platform
Lefkothea C. Papadopoulou - One of the best experts on this subject based on the ideXlab platform.
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Intracellular delivery of full length recombinant human mitochondrial L-SCO2 protein into the mitochondria of permanent cell lines and SCO2 deficient patient's primary cells.
Biochimica et biophysica acta, 2010Co-Authors: Parthena Foltopoulou, Asterios S. Tsiftsoglou, Ioannis Bonovolias, Alexandra T. Ingendoh, Lefkothea C. PapadopoulouAbstract:Mutations in human SCO2 gene, encoding the mitochondrial inner membrane SCO2 protein, have been found to be responsible for fatal infantile cardioencephalomyopathy and cytochrome c oxidase (COX) deficiency. One potentially fruitful therapeutic approach for this mitochondrial disorder should be considered the production of human recombinant full length L-SCO2 protein and its deliberate transduction into the mitochondria. Recombinant L-SCO2 protein, fused with TAT, a Protein Transduction Domain (PTD), was produced in bacteria and purified from inclusion bodies (IBs). Following solubilisation with l-arginine, this fusion L-SCO2 protein was transduced in cultured mammalian cells of different origin (U-87 MG, T24, K-562, and patient's primary fibroblasts) and assessed for stability, transduction into mitochondria, processing and impact on recovery of COX activity. Our results indicate that: a) l-Arg solution was effective in solubilising recombinant fusion L-SCO2 protein, derived from IBs; b) fusion L-SCO2 protein was delivered successfully via a time- and concentration-dependent process into the mitochondria of human U-87 MG and T24 cells; c) fusion L-SCO2 protein was also transduced in human K-562 cells, transiently depleted of SCO2 transcripts and thus COX deficient; transduction of this fusion protein led to partial recovery of COX activity in such cells; d) [(35)S]Methionine-labelled fusion L-SCO2 protein, produced in a cell free transcription/translation system and incubated with intact isolated mitochondria derived from K-562 cells, was efficiently processed to yield the corresponding mature SCO2 protein, thus justifying the potential of the transduced fusion L-SCO2 protein to successfully activate COX holoenzyme; and finally, e) recombinant fusion L-SCO2 protein was successfully transduced into the mitochondria of primary fibroblasts derived from SCO2/COX deficient patient and facilitated recovery of COX activity. These findings provide the rationale of delivering recombinant proteins via PTD technology as a model for therapeutic approach of mitochondrial disorders.
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differential features of patients with mutations in two cox assembly genes surf 1 and SCO2
Annals of Neurology, 2000Co-Authors: Carolyn M. Sue, Kurenai Tanji, Lefkothea C. Papadopoulou, Charalampos Karadimas, Nicoletta Checcarelli, Francesco Pallotti, F. L. Guo, S. Shanske, Michio Hirano, Darryl C. De VivoAbstract:We screened 41 patients with undiagnosed encephalomyopathies and cytochrome c oxidase (COX) deficiency for mutations in two COX assembly genes, SURF-1 and SCO2; 6 patients had mutations in SURF-1 and 3 had mutations in SCO2. All of the mutations in SURF-1 were small-scale rearrangements (deletions/insertions); 3 patients were homozygotes and the other 3 were compound heterozygotes. All patients with SCO2 mutations were compound heterozygotes for nonsense or missense mutations. All of the patients with mutations in SURF-1 had Leigh syndrome, whereas the 3 patients with SCO2 mutations had a combination of encephalopathy and hypertrophic cardiomyopathy, and the neuropathology did not show the typical features of Leigh syndrome. In patients with SCO2 mutations, onset was earlier and the clinical course and progression to death more rapid than in patients with SURF-1 mutations. In addition, biochemical and morphological studies showed that the COX deficiency was more severe in patients with SCO2 mutations. Immunohistochemical studies suggested that SURF-1 mutations result in similarly reduced levels of mitochondrial-encoded and nuclear-encoded COX subunits, whereas SCO2 mutations affected mitochondrial-encoded subunits to a greater degree. We conclude that patients with mutations in SURF-1 and SCO2 genes have distinct phenotypes despite the common biochemical defect of COX activity.
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Differential features of patients with mutations in two COX assembly genes, SURF‐1 and SCO2
Annals of neurology, 2000Co-Authors: Carolyn M. Sue, Kurenai Tanji, Lefkothea C. Papadopoulou, Charalampos Karadimas, Nicoletta Checcarelli, Francesco Pallotti, F. L. Guo, S. Shanske, Michio Hirano, Darryl C. De VivoAbstract:We screened 41 patients with undiagnosed encephalomyopathies and cytochrome c oxidase (COX) deficiency for mutations in two COX assembly genes, SURF-1 and SCO2; 6 patients had mutations in SURF-1 and 3 had mutations in SCO2. All of the mutations in SURF-1 were small-scale rearrangements (deletions/insertions); 3 patients were homozygotes and the other 3 were compound heterozygotes. All patients with SCO2 mutations were compound heterozygotes for nonsense or missense mutations. All of the patients with mutations in SURF-1 had Leigh syndrome, whereas the 3 patients with SCO2 mutations had a combination of encephalopathy and hypertrophic cardiomyopathy, and the neuropathology did not show the typical features of Leigh syndrome. In patients with SCO2 mutations, onset was earlier and the clinical course and progression to death more rapid than in patients with SURF-1 mutations. In addition, biochemical and morphological studies showed that the COX deficiency was more severe in patients with SCO2 mutations. Immunohistochemical studies suggested that SURF-1 mutations result in similarly reduced levels of mitochondrial-encoded and nuclear-encoded COX subunits, whereas SCO2 mutations affected mitochondrial-encoded subunits to a greater degree. We conclude that patients with mutations in SURF-1 and SCO2 genes have distinct phenotypes despite the common biochemical defect of COX activity.
Dario Leister - One of the best experts on this subject based on the ideXlab platform.
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snowy cotyledon 2 promotes chloroplast development and has a role in leaf variegation in both lotus japonicus and arabidopsis thaliana
Molecular Plant, 2017Co-Authors: Omar Sandovalibanez, Junyi Su, Jens Stougaard, Nicola Zagari, Manuel Rodriguezconcepcion, Dario Leister, Niels Sandal, Mathias PribilAbstract:Abstract Plants contain various factors that transiently interact with subunits or intermediates of the thylakoid multiprotein complexes, promoting their stable association and integration. Hence, assembly factors are essential for chloroplast development and the transition from heterotrophic to phototrophic growth. Snowy cotyledon 2 (SCO2) is a DNAJ-like protein involved in thylakoid membrane biogenesis and interacts with the light-harvesting chlorophyll-binding protein LHCB1. In Arabidopsis thaliana , SCO2 function was previously reported to be restricted to cotyledons. Here we show that disruption of SCO2 in Lotus japonicus results not only in paler cotyledons but also in variegated true leaves. Furthermore, smaller and pale-green true leaves can also be observed in A. thaliana SCO2 ( atSCO2 ) mutants under short-day conditions. In both species, SCO2 is required for proper accumulation of PSII–LHCII complexes. In contrast to other variegated mutants, inhibition of chloroplastic translation strongly affects L. japonicus SCO2 mutant development and fails to suppress their variegated phenotype. Moreover, inactivation of the suppressor of variegation AtClpR1 in the atSCO2 background results in an additive double-mutant phenotype with variegated true leaves. Taken together, our results indicate that SCO2 plays a distinct role in PSII assembly or repair and constitutes a novel factor involved in leaf variegation.
Toshifumi Matsuoka - One of the best experts on this subject based on the ideXlab platform.
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estimation of co2 saturation during both co2 drainage and imbibition processes based on both seismic velocity and electrical resistivity measurements
Geophysical Journal International, 2013Co-Authors: Jongwook Kim, Myung Jin Nam, Toshifumi MatsuokaAbstract:SUMMARY In order to monitor injected carbon dioxide (CO2), simultaneous measurements of seismic velocity and electrical resistivity are employed during the drainage (CO2 injection) and imbibition (water injection) processes of a Berea sandstone. Supercritical CO2 (10 MPa at 40 o C) was injected into a water-saturated Berea sandstone in the drainage stage and monitored via simultaneous measurements. After the injection of supercritical CO2, fresh distilled water was injected into the CO2-injected sandstone during the imbibition stage. Electrical resistivity and P-wave velocity measurements acquired during the drainage and imbibition stages were employed to evaluate CO2 saturations (SCO2) based on the resistivity index and the Gassmann fluid-substitution equations, respectively. Comparing estimated values for SCO2 saturation against those from volume-derived SCO2, based on analysis on injected and drained fluid volumes in the drainage process, we conclude that Gassmann‐Brie and resistivity index are suitable for the evaluation based on P-wave velocity and electrical resistivity, respectively. Rt-based estimation properly tracks the variation in SCO2 even when SCO2 is large (>0.15), while Vp-based estimation is sensitive to the variation in SCO2 when SCO2 is small ( 0.1), while properly estimating SCO2 when SCO2 is small (<0.1). Monitoring the CO2 imbibition process confirms residual CO2 saturation within the sample.
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Estimation of CO2 saturation during both CO2 drainage and imbibition processes based on both seismic velocity and electrical resistivity measurements
Geophysical Journal International, 2013Co-Authors: Jongwook Kim, Myung Jin Nam, Toshifumi MatsuokaAbstract:SUMMARY In order to monitor injected carbon dioxide (CO2), simultaneous measurements of seismic velocity and electrical resistivity are employed during the drainage (CO2 injection) and imbibition (water injection) processes of a Berea sandstone. Supercritical CO2 (10 MPa at 40 o C) was injected into a water-saturated Berea sandstone in the drainage stage and monitored via simultaneous measurements. After the injection of supercritical CO2, fresh distilled water was injected into the CO2-injected sandstone during the imbibition stage. Electrical resistivity and P-wave velocity measurements acquired during the drainage and imbibition stages were employed to evaluate CO2 saturations (SCO2) based on the resistivity index and the Gassmann fluid-substitution equations, respectively. Comparing estimated values for SCO2 saturation against those from volume-derived SCO2, based on analysis on injected and drained fluid volumes in the drainage process, we conclude that Gassmann‐Brie and resistivity index are suitable for the evaluation based on P-wave velocity and electrical resistivity, respectively. Rt-based estimation properly tracks the variation in SCO2 even when SCO2 is large (>0.15), while Vp-based estimation is sensitive to the variation in SCO2 when SCO2 is small ( 0.1), while properly estimating SCO2 when SCO2 is small (
Darryl C. De Vivo - One of the best experts on this subject based on the ideXlab platform.
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differential features of patients with mutations in two cox assembly genes surf 1 and SCO2
Annals of Neurology, 2000Co-Authors: Carolyn M. Sue, Kurenai Tanji, Lefkothea C. Papadopoulou, Charalampos Karadimas, Nicoletta Checcarelli, Francesco Pallotti, F. L. Guo, S. Shanske, Michio Hirano, Darryl C. De VivoAbstract:We screened 41 patients with undiagnosed encephalomyopathies and cytochrome c oxidase (COX) deficiency for mutations in two COX assembly genes, SURF-1 and SCO2; 6 patients had mutations in SURF-1 and 3 had mutations in SCO2. All of the mutations in SURF-1 were small-scale rearrangements (deletions/insertions); 3 patients were homozygotes and the other 3 were compound heterozygotes. All patients with SCO2 mutations were compound heterozygotes for nonsense or missense mutations. All of the patients with mutations in SURF-1 had Leigh syndrome, whereas the 3 patients with SCO2 mutations had a combination of encephalopathy and hypertrophic cardiomyopathy, and the neuropathology did not show the typical features of Leigh syndrome. In patients with SCO2 mutations, onset was earlier and the clinical course and progression to death more rapid than in patients with SURF-1 mutations. In addition, biochemical and morphological studies showed that the COX deficiency was more severe in patients with SCO2 mutations. Immunohistochemical studies suggested that SURF-1 mutations result in similarly reduced levels of mitochondrial-encoded and nuclear-encoded COX subunits, whereas SCO2 mutations affected mitochondrial-encoded subunits to a greater degree. We conclude that patients with mutations in SURF-1 and SCO2 genes have distinct phenotypes despite the common biochemical defect of COX activity.
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Differential features of patients with mutations in two COX assembly genes, SURF‐1 and SCO2
Annals of neurology, 2000Co-Authors: Carolyn M. Sue, Kurenai Tanji, Lefkothea C. Papadopoulou, Charalampos Karadimas, Nicoletta Checcarelli, Francesco Pallotti, F. L. Guo, S. Shanske, Michio Hirano, Darryl C. De VivoAbstract:We screened 41 patients with undiagnosed encephalomyopathies and cytochrome c oxidase (COX) deficiency for mutations in two COX assembly genes, SURF-1 and SCO2; 6 patients had mutations in SURF-1 and 3 had mutations in SCO2. All of the mutations in SURF-1 were small-scale rearrangements (deletions/insertions); 3 patients were homozygotes and the other 3 were compound heterozygotes. All patients with SCO2 mutations were compound heterozygotes for nonsense or missense mutations. All of the patients with mutations in SURF-1 had Leigh syndrome, whereas the 3 patients with SCO2 mutations had a combination of encephalopathy and hypertrophic cardiomyopathy, and the neuropathology did not show the typical features of Leigh syndrome. In patients with SCO2 mutations, onset was earlier and the clinical course and progression to death more rapid than in patients with SURF-1 mutations. In addition, biochemical and morphological studies showed that the COX deficiency was more severe in patients with SCO2 mutations. Immunohistochemical studies suggested that SURF-1 mutations result in similarly reduced levels of mitochondrial-encoded and nuclear-encoded COX subunits, whereas SCO2 mutations affected mitochondrial-encoded subunits to a greater degree. We conclude that patients with mutations in SURF-1 and SCO2 genes have distinct phenotypes despite the common biochemical defect of COX activity.
Klaus Apel - One of the best experts on this subject based on the ideXlab platform.
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the SCO2 protein disulphide isomerase is required for thylakoid biogenesis and interacts with lchb1 chlorophyll a b binding proteins which affects chlorophyll biosynthesis in arabidopsis seedlings
Plant Journal, 2012Co-Authors: Sandra K Tanz, Klaus Apel, Joachim Kilian, Christoffer Johnsson, Ian Small, Klaus Harter, Dierk Wanke, Barry J Pogson, Veronica AlbrechtAbstract:*† ‡ SUMMARY The process of chloroplast biogenesis requires a multitude of pathways and processes to establish chloroplast function. In cotyledons of seedlings, chloroplasts develop either directly from proplastids (also named eoplasts) or, if germinated in the dark, via etioplasts, whereas in leaves chloroplasts derive from proplastids in the apical meristem and are then multiplied by division. The snowy cotyledon 2, SCO2, mutations specifically disrupt chloroplast biogenesis in cotyledons. SCO2 encodes a chloroplast-localized protein disulphide isomerase, hypothesized to be involved in protein folding. Analysis of co-expressed genes with SCO2 revealed that genes with similar expression patterns encode chloroplast proteins involved in protein translation and in chlorophyll biosynthesis. Indeed, SCO2-1 accumulates increased levels of the chlorophyll precursor, protochlorophyllide, in both dark grown cotyledons and leaves. Yeast two-hybrid analyses demonstrated that SCO2 directly interacts with the chlorophyll-binding LHCB1 proteins, being confirmed in planta using bimolecular fluorescence complementation (BIFC). Furthermore, ultrastructural analysis of SCO2-1 chloroplasts revealed that formation and movement of transport vesicles from the inner envelope to the thylakoids is perturbed. SCO2 does not interact with the signal recognition particle proteins SRP54 and FtsY, which were shown to be involved in targeting of LHCB1 to the thylakoids. We hypothesize that SCO2 provides an alternative targeting pathway for light-harvesting chlorophyll binding (LHCB) proteins to the thylakoids via transport vesicles predominantly in cotyledons, with the signal recognition particle (SRP) pathway predominant in rosette leaves. Therefore, we propose that SCO2 is involved in the integration of LHCB1 proteins into the thylakoids that feeds back on the regulation of the tetrapyrrole biosynthetic pathway and nuclear gene expression.
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snowy cotyledon 2 the identification of a zinc finger domain protein essential for chloroplast development in cotyledons but not in true leaves
Plant Molecular Biology, 2008Co-Authors: Veronica Albrecht, Anke Ingenfeld, Klaus ApelAbstract:In cotyledons of etiolated seedlings light-dependent transformation of etioplasts to chloroplasts marks the transition from heterotrophic to autotrophic growth. Genetic factors required for this developmental step were identified by isolating mutants of Arabidopsis thaliana that were impaired in chloroplast development in cotyledons but not in true leaves. Several mutants with chlorophyll-deficient cotyledons were isolated and dubbed snowy cotyledon (sco). Here we describe the identification and detailed characterization of the snowy cotyledon 2 mutant. The mutated SCO2 gene was identified using a map-based cloning strategy. SCO2 was shown to encode a novel protein which contains a single DnaJ-like zinc finger domain. The SCO2 protein fused to GFP was shown to be present in chloroplasts. Inactivation of SCO2 has almost no detectable impact on the levels of transcripts encoding plastid-specific proteins but leads to a significant reduction of plastid protein levels. Even though transcripts of SCO2 have been found ubiquitously in green tissues as well as in roots phenotypic changes due to SCO2 inactivation are confined to cotyledons. The cotyledons in embryos of SCO2 are unaffected in their chloroplast biogenesis. Upon precocious germination seedlings of SCO2 and wild type are indistinguishable. The SCO2 mutation affects chloroplast biogenesis only at the end of dormancy during seed germination. The transition from heterotrophic to autotrophic growth is dramatically impaired in SCO2 when seedlings were kept in the dark for more than 5 days prior to light exposure.