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https://www.readbyqxmd.com/read/29208936/disulfide-driven-folding-for-a-conditionally-disordered-protein
#1
Hugo Fraga, Jordi Pujols, Marcos Gil-Garcia, Alicia Roque, Ganeko Bernardo-Seisdedos, Carlo Santambrogio, Joan-Josep Bech-Serra, Francesc Canals, Pau Bernadó, Rita Grandori, Oscar Millet, Salvador Ventura
Conditionally disordered proteins are either ordered or disordered depending on the environmental context. The substrates of the mitochondrial intermembrane space (IMS) oxidoreductase Mia40 are synthesized on cytosolic ribosomes and diffuse as intrinsically disordered proteins to the IMS, where they fold into their functional conformations; behaving thus as conditionally disordered proteins. It is not clear how the sequences of these polypeptides encode at the same time for their ability to adopt a folded structure and to remain unfolded...
December 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28978152/mitochondrial-markers-predict-recurrence-metastasis-and-tamoxifen-resistance-in-breast-cancer-patients-early-detection-of-treatment-failure-with-companion-diagnostics
#2
Federica Sotgia, Marco Fiorillo, Michael P Lisanti
Here, we used a data-mining and informatics approach to discover new biomarkers of resistance to hormonal therapy in breast cancer. More specifically, we investigated whether nuclear-encoded genes associated with mitochondrial biogenesis can be used to predict tumor recurrence, distant metastasis and treatment failure in high-risk breast cancer patients. Overall, this strategy allowed us to directly provide in silico validation of the prognostic value of these mitochondrial components in large and clinically relevant patient populations, with >15 years of follow-up data...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28965931/integrated-microarray-analysis-provided-a-new-insight-of-the-pathogenesis-of-parkinson-s-disease
#3
Ping Kong, Ping Lei, Shishuang Zhang, Dai Li, Jing Zhao, Benshu Zhang
BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease and the exact pathogenic mechanism remains mostly elusive. Our study aims to identify the key differentially expressed genes (DEGs) and up regulators in PD. METHODS: An integrated analysis of microarray studies of PD was performed to identify the DEGs in PD compared to normal control (NC). Based on these DEGs, we performed the functional annotation and transcriptional regulatory network constructions...
September 28, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28965584/identification-of-eight-copper-cu-uptake-related-genes-from-yellow-catfish-pelteobagrus-fulvidraco-and-their-tissue-expression-and-transcriptional-responses-to-dietborne-cu-exposure
#4
Jie Cheng, Zhi Luo, Guang-Hui Chen, Chuan-Chuan Wei, Mei-Qin Zhuo
The present working hypothesis is that absorption of dietary Cu is related to mRNA expressions of genes involved in Cu uptake and transport of the intestine in fish. To this end, the full-length cDNA sequences of eight Cu uptake related genes, including two isoforms of copper transporter genes (ctr1 and ctr2), three copper chaperone genes (atox1, ccs and cox17), two Cu-ATPase genes (atp7a and atp7b) and divalent metal ion transporter 1 (dmt1), were cloned and characterized in yellow catfish P. fulvidraco, respectively...
December 2017: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/28938148/intestinal-epithelial-cell-injury-induced-by-copper-containing-nanoparticles-in-piglets
#5
Hui Zhang, Xiaoxing Wu, Khalid Mehmood, Zhenyu Chang, Kun Li, Xiong Jiang, Fazul Nabi, Muhammad Ijaz, Mujeeb Ur Rehman, Muhammad Tariq Javed, Donghai Zhou
The nano copper has been widely used in modern clinical medicine practice. However, it has been noticed that nano copper particles induce cell injury and toxicity. The present study was designed to determine the effect of nano copper particles on cell injury of intestinal epithelial cells (IECs) in piglets. The IECs were treated with different doses of nano copper (5, 10, 20 and 40μg/ml) for 24-48h to observe cell injury and toxicity. Cell injury was measured based on morphological and other changes including oxidative stress and genes expression...
September 18, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28754844/mitochondrial-markers-predict-recurrence-metastasis-and-tamoxifen-resistance-in-breast-cancer-patients-early-detection-of-treatment-failure-with-companion-diagnostics
#6
Federica Sotgia, Marco Fiorillo, Michael P Lisanti
Here, we used a data-mining and informatics approach to discover new biomarkers of resistance to hormonal therapy in breast cancer. More specifically, we investigated whether nuclear-encoded genes associated with mitochondrial biogenesis can be used to predict tumor recurrence, distant metastasis and treatment failure in high-risk breast cancer patients. Overall, this strategy allowed us to directly provide in silico validation of the prognostic value of these mitochondrial components in large and clinically relevant patient populations, with >15 years of follow-up data...
July 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28357365/cox1-mutation-abrogates-need-for-cox23-in-cytochrome-c-oxidase-biogenesis
#7
Richard Dela Cruz, Mi-Young Jeong, Dennis R Winge
Cox23 is a known conserved assembly factor for cytochrome c oxidase, although its role in cytochrome c oxidase (CcO) biogenesis remains unresolved. To gain additional insights into its role, we isolated spontaneous suppressors of the respiratory growth defect in cox23∆ yeast cells. We recovered independent colonies that propagated on glycerol/lactate medium for cox23∆ cells at 37°C. We mapped these mutations to the mitochondrial genome and specifically to COX1 yielding an I(101)F substitution. The I(101)F Cox1 allele is a gain-of-function mutation enabling yeast to respire in the absence of Cox23...
June 30, 2016: Microbial Cell
https://www.readbyqxmd.com/read/27711126/integrated-left-ventricular-global-transcriptome-and-proteome-profiling-in-human-end-stage-dilated-cardiomyopathy
#8
Dilek Colak, Ayodele A Alaiya, Namik Kaya, Nzioka P Muiya, Olfat AlHarazi, Zakia Shinwari, Editha Andres, Nduna Dzimiri
AIMS: The disease pathways leading to idiopathic dilated cardiomyopathy (DCM) are still elusive. The present study investigated integrated global transcriptional and translational changes in human DCM for disease biomarker discovery. METHODS: We used identical myocardial tissues from five DCM hearts compared to five non-failing (NF) donor hearts for both transcriptome profiling using the ABI high-density oligonucleotide microarrays and proteome expression with One-Dimensional Nano Acquity liquid chromatography coupled with tandem mass spectrometry on the Synapt G2 system...
2016: PloS One
https://www.readbyqxmd.com/read/27539433/identification-of-binding-sites-of-cisplatin-to-human-copper-chaperone-protein-cox17-by-high-resolution-ft-icr-ms
#9
Lijie Li, Wei Guo, Kui Wu, Yao Zhao, Qun Luo, Qingwu Zhang, Jianan Liu, Shaoxiang Xiong, Fuyi Wang
RATIONALE: Cox17 is a key copper chaperone protein responsible for delivery of cuprous ions to mitochondria and has been demonstrated to be involved in the anticancer action of cisplatin. However, the binding sites of the drug to the protein have not yet been directly identified. METHODS: The recombinant protein apo-Cox172s-s , the functional state of Cox17 transferring Cu(I), was reacted with an excess of cisplatin to produce platinated Cox17 adducts, of which the platination sites were identified by high-resolution Fourier transform ion cyclotron tandem mass spectrometry (FT-ICR-MS/MS) through electron capture dissociation (ECD)...
August 2016: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/27235272/a-comparative-study-on-the-interactions-of-human-copper-chaperone-cox17-with-anticancer-organoruthenium-ii-complexes-and-cisplatin-by-mass-spectrometry
#10
Lijie Li, Wei Guo, Kui Wu, Xuelei Wu, Linhong Zhao, Yao Zhao, Qun Luo, Yuanyuan Wang, Yangzhong Liu, Qingwu Zhang, Fuyi Wang
Herein we report investigation of the interactions between anticancer organoruthenium complexes, [(η(6)-arene)Ru(en)(Cl)]PF6 (en=ethylenediamine, arene=p-cymene (1) or biphenyl (2)), and the human copper chaperone protein Cox17 by mass spectrometry with cisplatin as a reference. The electrospray ionization mass spectrometry (ESI-MS) results indicate much weaker binding of the ruthenium complexes than that of cisplatin to apo-Cox172s-s, the functional state of Cox17. Up to tetra-platinated Cox17 adducts were identified while only mono-ruthenated and a little amount of di-ruthenated Cox17 adducts were detected even for the reactions with 10-fold excess of the Ru complexes...
August 2016: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/27065250/the-evolution-of-micos-ancestral-and-derived-functions-and-interactions
#11
Sergio A Muñoz-Gómez, Claudio H Slamovits, Joel B Dacks, Jeremy G Wideman
The MItochondrial Contact Site and Cristae Organizing System (MICOS) is required for the biogenesis and maintenance of mitochondrial cristae as well as the proper tethering of the mitochondrial inner and outer membranes. We recently demonstrated that the core components of MICOS, Mic10 and Mic60, are near-ubiquitous eukaryotic features inferred to have been present in the last eukaryote common ancestor. We also showed that Mic60 could be traced to α-proteobacteria, which suggests that mitochondrial cristae evolved from α-proteobacterial intracytoplasmic membranes...
November 2015: Communicative & Integrative Biology
https://www.readbyqxmd.com/read/26616059/characterization-and-sub-cellular-localization-of-galnac-binding-proteins-isolated-from-human-hepatic-stellate-cells
#12
Yaogang Zhong, Jing Zhang, Hanjie Yu, Jiaxu Zhang, Xiu-Xuan Sun, Wentian Chen, Huijie Bian, Zheng Li
Although the expression levels of total GalNAc-binding proteins (GNBPs) were up-regulated significantly in human hepatic stellate cells (HSCs) activated with transforming growth factor-β1(TGF-β1), yet little is known about the precise types, distribution and sub-cellular localization of the GNBPs in HSCs. Here, 264 GNBPs from the activated HSCs and 257 GNBPs from the quiescent HSCs were identified and annotated. A total of 46 GNBPs were estimated to be significantly up-regulated and 40 GNBPs were estimated to be significantly down-regulated in the activated HSCs...
December 25, 2015: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/26493364/integrated-multi-omics-analyses-reveal-the-pleiotropic-nature-of-the-control-of-gene-expression-by-puf3p
#13
Christopher J Kershaw, Joseph L Costello, David Talavera, William Rowe, Lydia M Castelli, Paul F G Sims, Christopher M Grant, Mark P Ashe, Simon J Hubbard, Graham D Pavitt
The PUF family of RNA-binding proteins regulate gene expression post-transcriptionally. Saccharomyces cerevisiae Puf3p is characterised as binding nuclear-encoded mRNAs specifying mitochondrial proteins. Extensive studies of its regulation of COX17 demonstrate its role in mRNA decay. Using integrated genome-wide approaches we define an expanded set of Puf3p target mRNAs and quantitatively assessed the global impact of loss of PUF3 on gene expression using mRNA and polysome profiling and quantitative proteomics...
October 23, 2015: Scientific Reports
https://www.readbyqxmd.com/read/26474410/the-features-of-copper-metabolism-in-the-rat-liver-during-development
#14
Yulia A Zatulovskaia, Ekaterina Y Ilyechova, Ludmila V Puchkova
Strong interest in copper homeostasis is due to the fact that copper is simultaneously a catalytic co-factor of the vital enzymes, a participant in signaling, and a toxic agent provoking oxidative stress. In mammals, during development copper metabolism is conformed to two types. In embryonic type copper metabolism (ETCM), newborns accumulate copper to high level in the liver because its excretion via bile is blocked; and serum copper concentration is low because ceruloplasmin (the main copper-containing protein of plasma) gene expression is repressed...
2015: PloS One
https://www.readbyqxmd.com/read/26436309/the-cytochrome-c-oxidase-biogenesis-factor-atcox17-modulates-stress-responses-in-arabidopsis
#15
Lucila Garcia, Elina Welchen, Uta Gey, Agustín L Arce, Iris Steinebrunner, Daniel H Gonzalez
COX17 is a soluble protein from the mitochondrial intermembrane space that participates in the transfer of copper for cytochrome c oxidase (COX) assembly in eukaryotic organisms. In this work, we studied the function of both Arabidopsis thaliana AtCOX17 genes using plants with altered expression levels of these genes. Silencing of AtCOX17-1 in a cox17-2 knockout background generates plants with smaller rosettes and decreased expression of genes involved in the response of plants to different stress conditions, including several genes that are induced by mitochondrial dysfunctions...
March 2016: Plant, Cell & Environment
https://www.readbyqxmd.com/read/25940911/ultramild-protein-mediated-click-chemistry-creates-efficient-oligonucleotide-probes-for-targeting-and-detecting-nucleic-acids
#16
Lina J Nåbo, Charlotte S Madsen, Knud J Jensen, Jacob Kongsted, Kira Astakhova
Functionalized synthetic oligonucleotides are finding growing applications in research, clinical studies, and therapy. However, it is not easy to prepare them in a biocompatible and highly efficient manner. We report a new strategy to synthesize oligonucleotides with promising nucleic acid targeting and detection properties. We focus in particular on the pH sensitivity of these new probes and their high target specificity. For the first time, human copper(I)-binding chaperon Cox17 was applied to effectively catalyze click labeling of oligonucleotides...
May 26, 2015: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/25918166/cox17-protein-is-an-auxiliary-factor-involved-in-the-control-of-the-mitochondrial-contact-site-and-cristae-organizing-system
#17
Magdalena Chojnacka, Agnieszka Gornicka, Silke Oeljeklaus, Bettina Warscheid, Agnieszka Chacinska
The mitochondrial contact site and cristae organizing system (MICOS) is a recently discovered protein complex that is crucial for establishing and maintaining the proper inner membrane architecture and contacts with the outer membrane of mitochondria. The ways in which the MICOS complex is assembled and its integrity is regulated remain elusive. Here, we report a direct link between Cox17, a protein involved in the assembly of cytochrome c oxidase, and the MICOS complex. Cox17 interacts with Mic60, thereby modulating MICOS complex integrity...
June 12, 2015: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/25451030/mia40-combines-thiol-oxidase-and-disulfide-isomerase-activity-to-efficiently-catalyze-oxidative-folding-in-mitochondria
#18
Johanna R Koch, Franz X Schmid
Mia40 (a mitochondrial import and assembly protein) catalyzes disulfide bond formation in proteins in the mitochondrial intermembrane space. By using Cox17 (a mitochondrial copper-binding protein) as a natural substrate, we discovered that, in the presence of Mia40, the formation of native disulfides is strongly favored. The catalytic mechanism of Mia40 involves a functional interplay between the chaperone site and the catalytic disulfide. Mia40 forms a specific native disulfide in Cox17 much more rapidly than other disulfides, in particular, non-native ones, which originates from the recently described high affinity for hydrophobic regions near target cysteines and the long lifetime of the mixed disulfide...
December 12, 2014: Journal of Molecular Biology
https://www.readbyqxmd.com/read/25447123/identification-and-initial-characterisation-of-a-plasmodium-falciparum-cox17-copper-metallochaperone
#19
David L Choveaux, Robert G E Krause, Jude M Przyborski, J P Dean Goldring
Copper is an essential micronutrient for all living organisms as an important catalytic co-factor for key enzymes. In higher eukaryotes intracellular copper is distributed by copper metallochaperones. Copper chelators such as neocuproine and tetrathiomolybdate inhibit Plasmodium falciparum erythrocytic development, indicating a requirement for copper by the parasite. A screen of the P. falciparum genome database identified eight potential copper-requiring protein orthologs, including four candidate copper metallochaperones implicated in the delivery of copper to cytochrome-c oxidase...
January 2015: Experimental Parasitology
https://www.readbyqxmd.com/read/25107896/vascular-endothelial-growth-factor-recovers-suppressed-cytochrome-c-oxidase-activity-by-restoring-copper-availability-in-hypertrophic-cardiomyocytes
#20
Miao Sun, Xiao Zuo, Rui Li, Tao Wang, Y James Kang
Cardiomyocyte hypertrophy induced by phenylepherine (PE) is accompanied by depression of cytochrome c oxidase (COX) activity. Vascular endothelial growth factor (VEGF) recovers the suppressed COX activity and reverses cardiomyocyte hypertrophy. Because PE causes intracellular copper (Cu) depletion and COX activity is Cu-dependent, the present study was undertaken to test the hypothesis that VEGF recovers suppressed COX activity by restoring Cu availability. Primary cultures of neonatal rat cardiomyocytes were treated with PE at a final concentration of 100 µmol/L in cultures for 48 h to induce cell hypertrophy...
December 2014: Experimental Biology and Medicine
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