DOCSLIB.ORG

UC San Diego Electronic Theses and Dissertations

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
UC San Diego Electronic Theses and Dissertations UC San Diego UC San Diego Electronic Theses and Dissertations Title Genome-Scale Reconstruction and Analysis of Eukaryotic Metabolic Networks Permalink https://escholarship.org/uc/item/5rq7d96x Author Hurlen, Natalie Christine Publication Date 2016-07-30 Supplemental Material https://escholarship.org/uc/item/5rq7d96x#supplemental Peer reviewed|Thesis/dissertation eScholarship.org Powered by the California Digital Library University of California UNIVERSITY OF CALIFORNIA, SAN DIEGO GENOME-SCALE RECONSTRUCTION AND ANALYSIS OF EUKARYOTIC METABOLIC NETWORKS A Dissertation submitted in partial satisfaction of the requirements for the degree Doctor of Philosophy in Bioengineering by Natalie Christine Hurlen Committee in charge: Professor Bernhard Ø. Palsson, Chair Professor Edward A. Dennis Professor Jeffrey D. Esko Professor Andrew D. McCulloch Professor Lanping Amy Sung 2006 Copyright Natalie Christine Hurlen, 2006 All rights reserved. The Dissertation of Natalie Christine Hurlen is approved, and it is acceptable in quality and form for publication on microfilm: Chair University of California, San Diego 2006 iii This Dissertation is dedicated to Mom, Pops, Mike, and “the boys” My dearest Erik and the Hurlen family and is in loving memory of Bohdan and Olga Chapla Henry and Eleanor Duarte iv We've called the human genome the book of life, but it's really three books: a history book, a shop manual and parts list, and a textbook of medicine more profoundly detailed than ever. Francis Collins, Director of the National Human Genome Research Institute v TABLE OF CONTENTS Signature Page .............................................................................................................iii Dedication.....................................................................................................................iv Epigraph........................................................................................................................v Table of Contents.........................................................................................................vi List of Figures ..............................................................................................................xi List of Tables..............................................................................................................xiv Preface…………………………………………………………………………........ xiv Acknowledgments......................................................................................................xvi Vita…………..............................................................................................................xix Abstract……………………………………………………………………………...xxi CHAPTER 1: INTRODUCTION ............................................................................... 1 1.1 What is systems biology? ......................................................................................... 1 1.2 Network reconstruction ............................................................................................ 1 1.3 Dissertation overview............................................................................................... 3 vi CHAPTER 2: TOOLS FOR GENOME-SCALE RECONSTRUCTION AND ANALYSIS.................................................................................................................... 6 2.1 Reconstruction resources.......................................................................................... 6 2.1.1 Genome annotation databases ................................................................... 6 2.1.2 Enzyme, reaction, and pathway databases ................................................ 7 2.1.3 Textbooks and review articles................................................................... 8 2.2 Constraint-based modeling....................................................................................... 8 2.2.1 Flux balance analysis................................................................................. 9 2.2.2 Phase planes and shadow price analysis.................................................. 10 2.2.3 In silico gene deletions ............................................................................ 11 CHAPTER 3: GENOME-SCALE RECONSTRUCTION OF THE SACCHAROMYCES CEREVISIAE METABOLIC NETWORK.......................... 15 3.1 Previous models of S. cerevisiae metabolism ........................................................ 15 3.2 Reconstruction of S. cerevisiae iND750 ................................................................ 17 3.2.1 Reconstruction procedure........................................................................ 17 3.2.2 Summary of S. cerevisiae iND750 .......................................................... 20 3.3 Validation of S. cerevisiae iND750 with a large-scale gene deletion study .......... 24 3.3.1 Comparison of in silico and in vitro growth phenotypes ........................ 24 vii 3.3.2 Analysis of false predictions by pathway and compartment................... 25 3.3.3 Analysis of false predictions by source................................................... 27 3.4 Conclusions ............................................................................................................ 36 CHAPTER 4: INTEGRATED ANALYSIS OF SACCHAROMYCES CEREVISIAE METABOLIC PHENOTYPES ........................................................ 50 4.1 In silico characterization of metabolic phenotypes ................................................ 50 4.1.1 S. cerevisiae phenotypic phase plane ...................................................... 51 4.1.2 Simulation of optimal metabolic phenotypes.......................................... 52 4.1.3 Further characterization of oxidative-fermentative phases ..................... 54 4.2 Integration of experimental data and in silico predictions ..................................... 56 4.3 Conclusions ............................................................................................................ 57 CHAPTER 5: GENOME-SCALE RECONSTRUCTION OF THE GLOBAL HUMAN METABOLIC NETWORK ...................................................................... 63 5.1 Previous models of mammalian metabolism.......................................................... 63 5.1.1 Small-scale, cell-specific metabolic models............................................ 64 5.1.2 Mammalian genome sequencing and the first genome-scale model ....... 65 5.1.3 Top-down reconstructions of human metabolism ................................... 66 5.2 Manual reconstruction of the global human metabolic network............................ 67 viii 5.2.1 Overall reconstruction strategy ............................................................... 67 5.2.2 Initial component list............................................................................... 68 5.2.3 Curation of network content.................................................................... 68 5.2.4 Functional validation and gap analysis ................................................... 72 5.2.5 The result, H. sapiens Recon 1................................................................ 72 5.3 Knowledge landscapes ........................................................................................... 74 5.4 Conclusions ............................................................................................................ 76 CHAPTER 6: GENE EXPRESSION ANALYSIS IN THE CONTEXT OF A GENOME-SCALE NETWORK............................................................................... 97 6.1 Integrated analysis of skeletal muscle metabolism ................................................ 97 6.1.1 The obesity epidemic............................................................................... 98 6.1.2 Metabolic gene expression in obese skeletal muscle .............................. 99 6.2 Tailoring the global metabolic network with pathway analysis........................... 103 6.3 Conclusions .......................................................................................................... 106 CHAPTER 7: CONCLUSIONS.............................................................................. 122 7.1 Contributions to the field...................................................................................... 123 7.1.1 Advancements in reconstructing eukaryotic metabolic networks......... 123 ix 7.1.2 Identification of metabolic knowledge gaps.......................................... 124 7.1.3 Integrated analysis of metabolic phenotypes......................................... 124 7.2 What’s next for S. cerevisiae iND750 and H. sapiens Recon 1? ......................... 125 7.3 Improving genome-scale reconstruction and analysis of eukaryotes................... 127 7.3.1 Enhancing component representations.................................................. 127 7.3.2 Improving communication with the research community..................... 130 7.3.3 Fine-tuning integration of gene-expression data................................... 130 7.4 Concluding remarks.............................................................................................. 132 BIBLIOGRAPHY..................................................................................................... 136 x LIST OF FIGURES Figure 1.1: The hierarchical relationship of network components.................................5 Figure 2.1: Overview of constraint-based modeling. ...................................................14 Figure 3.1: Overall reconstruction strategy for S. cerevisiae iND750. ........................38
Load more

Recommended publications
  • Characterization of the Ergosterol Biosynthesis Pathway in Ceratocystidaceae
    Journal of Fungi Article Characterization of the Ergosterol Biosynthesis Pathway in Ceratocystidaceae Mohammad Sayari 1,2,*, Magrieta A. van der Nest 1,3, Emma T. Steenkamp 1, Saleh Rahimlou 4 , Almuth Hammerbacher 1 and Brenda D. Wingfield 1 1 Department of Biochemistry, Genetics and Microbiology, Forestry and Agricultural Biotechnology Institute (FABI), University of Pretoria, Pretoria 0002, South Africa; [email protected] (M.A.v.d.N.); [email protected] (E.T.S.); [email protected] (A.H.); brenda.wingfi[email protected] (B.D.W.) 2 Department of Plant Science, University of Manitoba, 222 Agriculture Building, Winnipeg, MB R3T 2N2, Canada 3 Biotechnology Platform, Agricultural Research Council (ARC), Onderstepoort Campus, Pretoria 0110, South Africa 4 Department of Mycology and Microbiology, University of Tartu, 14A Ravila, 50411 Tartu, Estonia; [email protected] * Correspondence: [email protected]; Fax: +1-204-474-7528 Abstract: Terpenes represent the biggest group of natural compounds on earth. This large class of organic hydrocarbons is distributed among all cellular organisms, including fungi. The different classes of terpenes produced by fungi are mono, sesqui, di- and triterpenes, although triterpene ergosterol is the main sterol identified in cell membranes of these organisms. The availability of genomic data from members in the Ceratocystidaceae enabled the detection and characterization of the genes encoding the enzymes in the mevalonate and ergosterol biosynthetic pathways. Using Citation: Sayari, M.; van der Nest, a bioinformatics approach, fungal orthologs of sterol biosynthesis genes in nine different species M.A.; Steenkamp, E.T.; Rahimlou, S.; of the Ceratocystidaceae were identified.
    [Show full text]
  • The Molecular Karyotype of 25 Clinical-Grade Human Embryonic Stem Cell Lines Received: 07 August 2015 1 1 2 3,4 Accepted: 27 October 2015 Maurice A
    www.nature.com/scientificreports OPEN The Molecular Karyotype of 25 Clinical-Grade Human Embryonic Stem Cell Lines Received: 07 August 2015 1 1 2 3,4 Accepted: 27 October 2015 Maurice A. Canham , Amy Van Deusen , Daniel R. Brison , Paul A. De Sousa , 3 5 6 5 7 Published: 26 November 2015 Janet Downie , Liani Devito , Zoe A. Hewitt , Dusko Ilic , Susan J. Kimber , Harry D. Moore6, Helen Murray3 & Tilo Kunath1 The application of human embryonic stem cell (hESC) derivatives to regenerative medicine is now becoming a reality. Although the vast majority of hESC lines have been derived for research purposes only, about 50 lines have been established under Good Manufacturing Practice (GMP) conditions. Cell types differentiated from these designated lines may be used as a cell therapy to treat macular degeneration, Parkinson’s, Huntington’s, diabetes, osteoarthritis and other degenerative conditions. It is essential to know the genetic stability of the hESC lines before progressing to clinical trials. We evaluated the molecular karyotype of 25 clinical-grade hESC lines by whole-genome single nucleotide polymorphism (SNP) array analysis. A total of 15 unique copy number variations (CNVs) greater than 100 kb were detected, most of which were found to be naturally occurring in the human population and none were associated with culture adaptation. In addition, three copy-neutral loss of heterozygosity (CN-LOH) regions greater than 1 Mb were observed and all were relatively small and interstitial suggesting they did not arise in culture. The large number of available clinical-grade hESC lines with defined molecular karyotypes provides a substantial starting platform from which the development of pre-clinical and clinical trials in regenerative medicine can be realised.
    [Show full text]
  • A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
    Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated.
    [Show full text]
  • Cell Development and Peripheral Survival Heme Exporter FLVCR Is
    Heme Exporter FLVCR Is Required for T Cell Development and Peripheral Survival Mary Philip, Scott A. Funkhouser, Edison Y. Chiu, Susan R. Phelps, Jeffrey J. Delrow, James Cox, Pamela J. Fink and This information is current as Janis L. Abkowitz of September 28, 2021. J Immunol 2015; 194:1677-1685; Prepublished online 12 January 2015; doi: 10.4049/jimmunol.1402172 http://www.jimmunol.org/content/194/4/1677 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2015/01/09/jimmunol.140217 Material 2.DCSupplemental http://www.jimmunol.org/ References This article cites 44 articles, 11 of which you can access for free at: http://www.jimmunol.org/content/194/4/1677.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision by guest on September 28, 2021 • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2015 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Heme Exporter FLVCR Is Required for T Cell Development and Peripheral Survival Mary Philip,*,† Scott A.
    [Show full text]
  • The Porcine Major Histocompatibility Complex and Related Paralogous Regions: a Review Patrick Chardon, Christine Renard, Claire Gaillard, Marcel Vaiman
    The porcine Major Histocompatibility Complex and related paralogous regions: a review Patrick Chardon, Christine Renard, Claire Gaillard, Marcel Vaiman To cite this version: Patrick Chardon, Christine Renard, Claire Gaillard, Marcel Vaiman. The porcine Major Histocom- patibility Complex and related paralogous regions: a review. Genetics Selection Evolution, BioMed Central, 2000, 32 (2), pp.109-128. 10.1051/gse:2000101. hal-00894302 HAL Id: hal-00894302 https://hal.archives-ouvertes.fr/hal-00894302 Submitted on 1 Jan 2000 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Genet. Sel. Evol. 32 (2000) 109–128 109 c INRA, EDP Sciences Review The porcine Major Histocompatibility Complex and related paralogous regions: a review Patrick CHARDON, Christine RENARD, Claire ROGEL GAILLARD, Marcel VAIMAN Laboratoire de radiobiologie et d’etude du genome, Departement de genetique animale, Institut national de la recherche agronomique, Commissariat al’energie atomique, 78352, Jouy-en-Josas Cedex, France (Received 18 November 1999; accepted 17 January 2000) Abstract – The physical alignment of the entire region of the pig major histocompat- ibility complex (MHC) has been almost completed. In swine, the MHC is called the SLA (swine leukocyte antigen) and most of its class I region has been sequenced.
    [Show full text]
  • Proteomic and Metabolomic Analyses of Mitochondrial Complex I-Deficient
    THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 287, NO. 24, pp. 20652–20663, June 8, 2012 © 2012 by The American Society for Biochemistry and Molecular Biology, Inc. Published in the U.S.A. Proteomic and Metabolomic Analyses of Mitochondrial Complex I-deficient Mouse Model Generated by Spontaneous B2 Short Interspersed Nuclear Element (SINE) Insertion into NADH Dehydrogenase (Ubiquinone) Fe-S Protein 4 (Ndufs4) Gene*□S Received for publication, November 25, 2011, and in revised form, April 5, 2012 Published, JBC Papers in Press, April 25, 2012, DOI 10.1074/jbc.M111.327601 Dillon W. Leong,a1 Jasper C. Komen,b1 Chelsee A. Hewitt,a Estelle Arnaud,c Matthew McKenzie,d Belinda Phipson,e Melanie Bahlo,e,f Adrienne Laskowski,b Sarah A. Kinkel,a,g,h Gayle M. Davey,g William R. Heath,g Anne K. Voss,a,h René P. Zahedi,i James J. Pitt,j Roman Chrast,c Albert Sickmann,i,k Michael T. Ryan,l Gordon K. Smyth,e,f,h b2 a,h,m,n3 David R. Thorburn, and Hamish S. Scott Downloaded from From the aMolecular Medicine Division, gImmunology Division, and eBioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia, the bMurdoch Childrens Research Institute, Royal Children’s Hospital and Department of Paediatrics, University of Melbourne, Parkville, Victoria 3052, Australia, the cDépartement de Génétique Médicale, Université de Lausanne, 1005 Lausanne, Switzerland, the dCentre for Reproduction and Development, Monash Institute of Medical Research, Clayton, Victoria 3168, Australia, the hDepartment of Medical Biology
    [Show full text]
  • What Is the Extent of the Role Played by Genetic Factors in Periodontitis?
    Perio Insight 4 Summer 2017 www.efp.org/perioinsight DEBATE EXPERT VIEW FOCUS RESEARCH Editor: Joanna Kamma What is the extent of the role played by genetic factors in periodontitis? Discover latest JCP research hile genetic factors are known to play a role in In a comprehensive overview of current knowledge, The Journal of Clinical Periodontology Wperiodontitis, a lot of research still needs to be they outline what is known today and discuss the (JCP) is the official scientific publication done to understand the mechanisms that are involved. most promising lines for future inquiry. of the European Federation of Indeed, the limited extent to which the genetic They note that the phenotypes of aggressive Periodontology (EFP). It publishes factors associated with periodontitis have been periodontitis (AgP) and chronic periodontitis (CP) may research relating to periodontal and peri- identified is “somewhat disappointing”, say Bruno not be as distinct as previously assumed because they implant diseases and their treatment. G. Loos and Deon P.M. Chin, from the Academic share genetic and other risk factors. The six JCP articles summarised in this Centre for Dentistry in Amsterdam. More on pages 2-5 edition of Perio Insight cover: (1) how periodontitis changes renal structures by oxidative stress and lipid peroxidation; (2) gingivitis and lifestyle influences on high-sensitivity C-reactive protein and interleukin 6 in adolescents; (3) the long-term efficacy of periodontal Researchers call regenerative therapies; (4) tooth loss in generalised aggressive periodontitis; (5) the association between diabetes for global action mellitus/hyperglycaemia and peri- implant diseases; (6) the efficacy of on periodontal collagen matrix seal and collagen sponge on ridge preservation in disease combination with bone allograft.
    [Show full text]
  • Human Blastocysts of Normal and Abnormal Karyotypes Display Distinct Transcriptome Profles Received: 16 March 2018 Frederick Licciardi1, Tenzin Lhakhang2, Yael G
    www.nature.com/scientificreports OPEN Human blastocysts of normal and abnormal karyotypes display distinct transcriptome profles Received: 16 March 2018 Frederick Licciardi1, Tenzin Lhakhang2, Yael G. Kramer3, Yutong Zhang4, Adriana Heguy4,5,6 & Accepted: 26 September 2018 Aristotelis Tsirigos 2,5,6 Published: xx xx xxxx Unveiling the transcriptome of human blastocysts can provide a wealth of important information regarding early embryonic ontology. Comparing the mRNA production of embryos with normal and abnormal karyotypes allows for a deeper understanding of the protein pathways leading to viability and aberrant fetal development. In addition, identifying transcripts specifc for normal or abnormal chromosome copy number could aid in the search for secreted substances that could be used to non- invasively identify embryos best suited for IVF embryo transfer. Using RNA-seq, we characterized the transcriptome of 71 normally developing human blastocysts that were karyotypically normal vs. trisomic or monosomic. Every monosomy and trisomy of the autosomal and sex chromosomes were evaluated, mostly in duplicate. We frst mapped the transcriptome of three normal embryos and found that a common core of more than 3,000 genes is expressed in all embryos. These genes represent pathways related to actively dividing cells, such as ribosome biogenesis and function, spliceosome, oxidative phosphorylation, cell cycle and metabolic pathways. We then compared transcriptome profles of aneuploid embryos to those of normal embryos. We observed that non-viable embryos had a large number of dysregulated genes, some showing a hundred-fold diference in expression. On the contrary, sex chromosome abnormalities, XO and XXX displayed transcriptomes more closely mimicking those embryos with 23 normal chromosome pairs.
    [Show full text]
  • Original Article Bioinformatic Analysis of Gene Expression Profile in Prostate Epithelial Cells Exposed to Low-Dose Cadmium
    Int J Clin Exp Med 2018;11(3):1669-1678 www.ijcem.com /ISSN:1940-5901/IJCEM0062792 Original Article Bioinformatic analysis of gene expression profile in prostate epithelial cells exposed to low-dose cadmium Qiling Liu1,2*, Rongqiang Zhang2*, Xiang Wang1, Peili Wang2, Xiaomei Ren2, Na Sun2, Xiangwen Li2, Xinhui Li2, Chunxu Hai1 1Department of Toxicology, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Op- erational Environment, Shaanxi Provincial Key Lab of Free Radical Biology and Medicine, School of Public Health, Medical University of The Air Force, Xi’an, Shaanxi 710032, China; 2Department of Epidemic and Health Statis- tics, The College of Public Health for The Shaanxi University of Chinese Medicine, Shaanxi 712046, China. *Equal contributors. Received July 25, 2017; Accepted February 5, 2018; Epub March 15, 2018; Published March 30, 2018 Abstract: Objective: This study was to identify key genes and biological pathways involved in responses of prostate epithelial cells after low-dose Cd exposure by using bioinformatic analysis. Methods: The gene chip data of prostate epithelial cells after low-dose Cd exposure were collected from public databases Gene Expression Omnibus. After identification of differentially expressed genes (DEGs), data were input into Qlucore Omics Explorer, Network Analyst, String, and Genclip for further analysis of gene expression profiles, protein-protein interactions (PPI) and protein- chemicals interactions, and critical molecular pathways. Results: A total of 384 DEGs were identified in Cd treated group compared with control group. The number of DEGs gradually decreased over time, with the largest number at 0 h. Furthermore, NDUFB5 (A, S), CYC1, UQCRB, ETFA (B), SNRPD2, and LSM3 (5, 6) were the hub proteins in the PPI network.
    [Show full text]
  • Low Abundance of the Matrix Arm of Complex I in Mitochondria Predicts Longevity in Mice
    ARTICLE Received 24 Jan 2014 | Accepted 9 Apr 2014 | Published 12 May 2014 DOI: 10.1038/ncomms4837 OPEN Low abundance of the matrix arm of complex I in mitochondria predicts longevity in mice Satomi Miwa1, Howsun Jow2, Karen Baty3, Amy Johnson1, Rafal Czapiewski1, Gabriele Saretzki1, Achim Treumann3 & Thomas von Zglinicki1 Mitochondrial function is an important determinant of the ageing process; however, the mitochondrial properties that enable longevity are not well understood. Here we show that optimal assembly of mitochondrial complex I predicts longevity in mice. Using an unbiased high-coverage high-confidence approach, we demonstrate that electron transport chain proteins, especially the matrix arm subunits of complex I, are decreased in young long-living mice, which is associated with improved complex I assembly, higher complex I-linked state 3 oxygen consumption rates and decreased superoxide production, whereas the opposite is seen in old mice. Disruption of complex I assembly reduces oxidative metabolism with concomitant increase in mitochondrial superoxide production. This is rescued by knockdown of the mitochondrial chaperone, prohibitin. Disrupted complex I assembly causes premature senescence in primary cells. We propose that lower abundance of free catalytic complex I components supports complex I assembly, efficacy of substrate utilization and minimal ROS production, enabling enhanced longevity. 1 Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne NE4 5PL, UK. 2 Centre for Integrated Systems Biology of Ageing and Nutrition, Newcastle University, Newcastle upon Tyne NE4 5PL, UK. 3 Newcastle University Protein and Proteome Analysis, Devonshire Building, Devonshire Terrace, Newcastle upon Tyne NE1 7RU, UK. Correspondence and requests for materials should be addressed to T.v.Z.
    [Show full text]
  • Association of Polymorphisms in the Telomere-Related Gene ACYP2 with Lung Cancer Risk in the Chinese Han Population
    www.impactjournals.com/oncotarget/ Oncotarget, 2016, Vol. 7, (No. 52), pp: 87473-87478 Research Paper Association of polymorphisms in the telomere-related gene ACYP2 with lung cancer risk in the Chinese Han population Nanzheng Chen1,*, Xiaomei Yang2,*, Wen Guo3, Jiangtao You1, Qifei Wu1, Guangjian Zhang1, Haijun Li1, Donghong Geng4, Tianbo Jin5, Junke Fu1, Yong Zhang1 1Department of Thoracic Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China 2Hospital 521 of China’s Ordnance Industry Group, Xi’an 710065, Shaanxi, China 3Inner Mongolia Medical University, Hohhot 010050, Inner Mongolia, China 4School of Continuing Education of Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China 5School of Life Sciences, Northwest University, Xi’an 710069, Shaanxi, China *These authors have contributed equally to this work Correspondence to: Junke Fu, email: [email protected] Yong Zhang, email: [email protected] Keywords: association study, lung cancer, telomere-related gene, single nucleotide polymorphisms (SNPs) Received: August 26, 2016 Accepted: October 14, 2016 Published: December 10, 2016 ABSTRACT Single nucleotide polymorphisms (SNPs) in the telomere-associated gene ACYP2 are associated with increased lung cancer risk. We explored the correlation between ACYP2 SNPs and lung cancer susceptibility in the Chinese Han population. A total of 554 lung cancer patients and 603 healthy controls were included in this study. Thirteen SNPs in ACYP2 were selected. Odds ratios (ORs) and 95% confidence intervals
    [Show full text]
  • Catalase: Bioinformatics Analyses of One of the Key Enzymes in Hydrogen Peroxide Metabolism
    6–71RYHPEHU 2019, Brno, Czech Republic Catalase: Bioinformatics analyses of one of the key enzymes in hydrogen peroxide metabolism Michaela Kameniarova, Romana Kopecka Department of Molecular Biology and Radiobiology Mendel University in Brno Zemedelska 1, 613 00 Brno CZECH REPUBLIC [email protected] Abstract: Catalases (CAT) are family of important antioxidant enzymes present in different isoforms and responsible for scavenging of hydrogen peroxide in almost all aerobically living organisms. In plants, they were found both in unicellular and multicellular species. Here, we performed bioinformatics analysis and analysed catalase evolutionary relationship and expression patterns. By comparing expression profiles of CATs and expression profiles of genes related to abiotic stimuli we found that almost 50% of light signalling genes were co-expressed with CATs. Further, by datamining in available resources and structural modelling we pinpointed candidate amino acid residues responsible for CAT thermostability. Key Words: catalase, H2O2, phylogenetics, abiotic stress, stability INTRODUCTION Plants contain several types of enzymes involved in H2O2 metabolism. These include catalases, ascorbate peroxidases, peroxiredoxins, glutathione/thioredoxin peroxidases, and glutathione S- transferases, but only catalases do not require additional cellular reductants (Mhamdi et al. 2010). Catalases are present almost in all aerobically respiring organisms. Within the cell environment, catalases are localized in all major sites of H2O2 production, mostly at peroxisomes, but they were detected in cytosol, mitochondria, and chloroplasts as well (Sharma and Ahmad 2014). Catalases (CAT, 1.11.1.6) are antioxidant enzymes that catalyse decomposition of hydrogen peroxide to water and molecular oxygen (2H2O2 → 2H2O + O2), an important process in defending cells against oxidative damage caused by reactive oxygen species (ROS; Alfonso-Prieto et al.
    [Show full text]