An Automated Pipeline for Inferring Variant-Driven Gene
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Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase -
Roles of Mitochondrial Respiratory Complexes During Infection Pedro Escoll, Lucien Platon, Carmen Buchrieser
Roles of Mitochondrial Respiratory Complexes during Infection Pedro Escoll, Lucien Platon, Carmen Buchrieser To cite this version: Pedro Escoll, Lucien Platon, Carmen Buchrieser. Roles of Mitochondrial Respiratory Complexes during Infection. Immunometabolism, Hapres, 2019, Immunometabolism and Inflammation, 1, pp.e190011. 10.20900/immunometab20190011. pasteur-02593579 HAL Id: pasteur-02593579 https://hal-pasteur.archives-ouvertes.fr/pasteur-02593579 Submitted on 15 May 2020 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. Distributed under a Creative Commons Attribution| 4.0 International License ij.hapres.com Review Roles of Mitochondrial Respiratory Complexes during Infection Pedro Escoll 1,2,*, Lucien Platon 1,2,3, Carmen Buchrieser 1,2,* 1 Institut Pasteur, Unité de Biologie des Bactéries Intracellulaires, 75015 Paris, France 2 CNRS-UMR 3525, 75015 Paris, France 3 Faculté des Sciences, Université de Montpellier, 34095 Montpellier, France * Correspondence: Pedro Escoll, Email: [email protected]; Tel.: +33-0-1-44-38-9540; Carmen Buchrieser, Email: [email protected]; Tel.: +33-0-1-45-68-8372. ABSTRACT Beyond oxidative phosphorylation (OXPHOS), mitochondria have also immune functions against infection, such as the regulation of cytokine production, the generation of metabolites with antimicrobial proprieties and the regulation of inflammasome-dependent cell death, which seem in turn to be regulated by the metabolic status of the organelle. -
Restoring Mitofusin Balance Prevents Axonal Degeneration in a Charcot-Marie-Tooth Type 2A Model
Amendment history: Corrigendum (January 2021) Restoring mitofusin balance prevents axonal degeneration in a Charcot-Marie-Tooth type 2A model Yueqin Zhou, … , Cathleen M. Lutz, Robert H. Baloh J Clin Invest. 2019;129(4):1756-1771. https://doi.org/10.1172/JCI124194. Research Article Neuroscience Graphical abstract Find the latest version: https://jci.me/124194/pdf RESEARCH ARTICLE The Journal of Clinical Investigation Restoring mitofusin balance prevents axonal degeneration in a Charcot-Marie-Tooth type 2A model Yueqin Zhou,1,2 Sharon Carmona,2 A.K.M.G. Muhammad,1,2 Shaughn Bell,1,2 Jesse Landeros,1,2 Michael Vazquez,1,2 Ritchie Ho,2 Antonietta Franco,3 Bin Lu,2 Gerald W. Dorn II,3 Shaomei Wang,2 Cathleen M. Lutz,4 and Robert H. Baloh1,2,5 1Center for Neural Science and Medicine, and 2Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA. 3Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA. 4The Jackson Laboratory, Bar Harbor, Maine, USA. 5Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, California, USA. Mitofusin-2 (MFN2) is a mitochondrial outer-membrane protein that plays a pivotal role in mitochondrial dynamics in most tissues, yet mutations in MFN2, which cause Charcot-Marie-Tooth disease type 2A (CMT2A), primarily affect the nervous system. We generated a transgenic mouse model of CMT2A that developed severe early onset vision loss and neurological deficits, axonal degeneration without cell body loss, and cytoplasmic and axonal accumulations of fragmented mitochondria. While mitochondrial aggregates were labeled for mitophagy, mutant MFN2 did not inhibit Parkin-mediated degradation, but instead had a dominant negative effect on mitochondrial fusion only when MFN1 was at low levels, as occurs in neurons. -
Cells Phenotype of Human Tolerogenic Dendritic Glycolytic
High Mitochondrial Respiration and Glycolytic Capacity Represent a Metabolic Phenotype of Human Tolerogenic Dendritic Cells This information is current as of September 26, 2021. Frano Malinarich, Kaibo Duan, Raudhah Abdull Hamid, Au Bijin, Wu Xue Lin, Michael Poidinger, Anna-Marie Fairhurst and John E. Connolly J Immunol published online 27 April 2015 http://www.jimmunol.org/content/early/2015/04/25/jimmun Downloaded from ol.1303316 Supplementary http://www.jimmunol.org/content/suppl/2015/04/25/jimmunol.130331 http://www.jimmunol.org/ Material 6.DCSupplemental Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on September 26, 2021 • 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. Published April 27, 2015, doi:10.4049/jimmunol.1303316 The Journal of Immunology High Mitochondrial Respiration and Glycolytic Capacity Represent a Metabolic Phenotype of Human Tolerogenic Dendritic Cells Frano Malinarich,*,† Kaibo Duan,† Raudhah Abdull Hamid,*,† Au Bijin,*,† Wu Xue Lin,*,† Michael Poidinger,† Anna-Marie Fairhurst,† and John E. -
Role of Cytochrome C Oxidase Nuclear-Encoded Subunits in Health and Disease
Physiol. Res. 69: 947-965, 2020 https://doi.org/10.33549/physiolres.934446 REVIEW Role of Cytochrome c Oxidase Nuclear-Encoded Subunits in Health and Disease Kristýna ČUNÁTOVÁ1, David PAJUELO REGUERA1, Josef HOUŠTĚK1, Tomáš MRÁČEK1, Petr PECINA1 1Department of Bioenergetics, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic Received February 2, 2020 Accepted September 13, 2020 Epub Ahead of Print November 2, 2020 Summary [email protected] and Tomáš Mráček, Department of Cytochrome c oxidase (COX), the terminal enzyme of Bioenergetics, Institute of Physiology CAS, Vídeňská 1083, 142 mitochondrial electron transport chain, couples electron transport 20 Prague 4, Czech Republic. E-mail: [email protected] to oxygen with generation of proton gradient indispensable for the production of vast majority of ATP molecules in mammalian Cytochrome c oxidase cells. The review summarizes current knowledge of COX structure and function of nuclear-encoded COX subunits, which may Energy demands of mammalian cells are mainly modulate enzyme activity according to various conditions. covered by ATP synthesis carried out by oxidative Moreover, some nuclear-encoded subunits possess tissue-specific phosphorylation apparatus (OXPHOS) located in the and development-specific isoforms, possibly enabling fine-tuning central bioenergetic organelle, mitochondria. OXPHOS is of COX function in individual tissues. The importance of nuclear- composed of five multi-subunit complexes embedded in encoded subunits is emphasized by recently discovered the inner mitochondrial membrane (IMM). Electron pathogenic mutations in patients with severe mitopathies. In transport from reduced substrates of complexes I and II to addition, proteins substoichiometrically associated with COX were cytochrome c oxidase (COX, complex IV, CIV) is found to contribute to COX activity regulation and stabilization of achieved by increasing redox potential of individual the respiratory supercomplexes. -
Human Mitochondrial Pathologies of the Respiratory Chain and ATP Synthase: Contributions from Studies of Saccharomyces Cerevisiae
life Review Human Mitochondrial Pathologies of the Respiratory Chain and ATP Synthase: Contributions from Studies of Saccharomyces cerevisiae Leticia V. R. Franco 1,2,* , Luca Bremner 1 and Mario H. Barros 2 1 Department of Biological Sciences, Columbia University, New York, NY 10027, USA; [email protected] 2 Department of Microbiology,Institute of Biomedical Sciences, Universidade de Sao Paulo, Sao Paulo 05508-900, Brazil; [email protected] * Correspondence: [email protected] Received: 27 October 2020; Accepted: 19 November 2020; Published: 23 November 2020 Abstract: The ease with which the unicellular yeast Saccharomyces cerevisiae can be manipulated genetically and biochemically has established this organism as a good model for the study of human mitochondrial diseases. The combined use of biochemical and molecular genetic tools has been instrumental in elucidating the functions of numerous yeast nuclear gene products with human homologs that affect a large number of metabolic and biological processes, including those housed in mitochondria. These include structural and catalytic subunits of enzymes and protein factors that impinge on the biogenesis of the respiratory chain. This article will review what is currently known about the genetics and clinical phenotypes of mitochondrial diseases of the respiratory chain and ATP synthase, with special emphasis on the contribution of information gained from pet mutants with mutations in nuclear genes that impair mitochondrial respiration. Our intent is to provide the yeast mitochondrial specialist with basic knowledge of human mitochondrial pathologies and the human specialist with information on how genes that directly and indirectly affect respiration were identified and characterized in yeast. Keywords: mitochondrial diseases; respiratory chain; yeast; Saccharomyces cerevisiae; pet mutants 1. -
Influenza-Specific Effector Memory B Cells Predict Long-Lived Antibody Responses to Vaccination in Humans
bioRxiv preprint doi: https://doi.org/10.1101/643973; this version posted February 18, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Influenza-specific effector memory B cells predict long-lived antibody responses to vaccination in humans Anoma Nellore1, Esther Zumaquero2, Christopher D. Scharer3, Rodney G. King2, Christopher M. Tipton4, Christopher F. Fucile5, Tian Mi3, Betty Mousseau2, John E. Bradley6, Fen Zhou2, Paul A. Goepfert1, Jeremy M. Boss3, Troy D. Randall6, Ignacio Sanz4, Alexander F. Rosenberg2,5, Frances E. Lund2 1Dept. of Medicine, Division of Infectious Disease, 2Dept of Microbiology, 5Informatics Institute, 6Dept. of Medicine, Division of Clinical Immunology and Rheumatology and at The University of Alabama at Birmingham, Birmingham, AL 35294 USA 3Dept. of Microbiology and Immunology and 4Department of Medicine, Division of Rheumatology Emory University, Atlanta, GA 30322, USA Correspondence should be addressed to: Frances E. Lund, PhD Charles H. McCauley Professor and Chair Dept of Microbiology University of Alabama at Birmingham 276 BBRB Box 11 1720 2nd Avenue South Birmingham AL 35294-2170 [email protected] SHORT RUNNING TITLE: Effector memory B cell development after influenza vaccination 1 bioRxiv preprint doi: https://doi.org/10.1101/643973; this version posted February 18, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract Seasonal influenza vaccination elicits hemagglutinin (HA)-specific CD27+ memory B cells (Bmem) that differ in expression of T-bet, BACH2 and TCF7. -
Heparanase Overexpression Induces Glucagon Resistance and Protects
Page 1 of 85 Diabetes Heparanase overexpression induces glucagon resistance and protects animals from chemically-induced diabetes Dahai Zhang1, Fulong Wang1, Nathaniel Lal1, Amy Pei-Ling Chiu1, Andrea Wan1, Jocelyn Jia1, Denise Bierende1, Stephane Flibotte1, Sunita Sinha1, Ali Asadi2, Xiaoke Hu2, Farnaz Taghizadeh2, Thomas Pulinilkunnil3, Corey Nislow1, Israel Vlodavsky4, James D. Johnson2, Timothy J. Kieffer2, Bahira Hussein1 and Brian Rodrigues1 1Faculty of Pharmaceutical Sciences, UBC, 2405 Wesbrook Mall, Vancouver, BC, Canada V6T 1Z3; 2Department of Cellular & Physiological Sciences, Life Sciences Institute, UBC, 2350 Health Sciences Mall, Vancouver, BC, Canada V6T 1Z3; 3Department of Biochemistry and Molecular Biology, Faculty of Medicine, Dalhousie University, 100 Tucker Park Road, Saint John, NB, Canada E2L 4L5; 4Cancer and Vascular Biology Research Center, Rappaport Faculty of Medicine, Technion, Haifa, Israel 31096 Running Title: Heparanase overexpression and the pancreatic islet Corresponding author: Dr. Brian Rodrigues Faculty of Pharmaceutical Sciences University of British Columbia, 2405 Wesbrook Mall, Vancouver, B.C., Canada V6T 1Z3 TEL: (604) 822-4758; FAX: (604) 822-3035 E-mail: [email protected] Key Words: Heparanase, heparan sulfate proteoglycan, glucose homeostasis, glucagon resistance, pancreatic islet, STZ Word Count: 4761 Total Number of DiabetesFigures: Publish 6 Ahead of Print, published online October 7, 2016 Diabetes Page 2 of 85 Abstract Heparanase, a protein with enzymatic and non-enzymatic properties, contributes towards disease progression and prevention. In the current study, a fortuitous observation in transgenic mice globally overexpressing heparanase (hep-tg) was the discovery of improved glucose homeostasis. We examined the mechanisms that contribute towards this improved glucose metabolism. Heparanase overexpression was associated with enhanced GSIS and hyperglucagonemia, in addition to changes in islet composition and structure. -
Electron Transport Chain Activity Is a Predictor and Target for Venetoclax Sensitivity in Multiple Myeloma
ARTICLE https://doi.org/10.1038/s41467-020-15051-z OPEN Electron transport chain activity is a predictor and target for venetoclax sensitivity in multiple myeloma Richa Bajpai1,7, Aditi Sharma 1,7, Abhinav Achreja2,3, Claudia L. Edgar1, Changyong Wei1, Arusha A. Siddiqa1, Vikas A. Gupta1, Shannon M. Matulis1, Samuel K. McBrayer 4, Anjali Mittal3,5, Manali Rupji 6, Benjamin G. Barwick 1, Sagar Lonial1, Ajay K. Nooka 1, Lawrence H. Boise 1, Deepak Nagrath2,3,5 & ✉ Mala Shanmugam 1 1234567890():,; The BCL-2 antagonist venetoclax is highly effective in multiple myeloma (MM) patients exhibiting the 11;14 translocation, the mechanistic basis of which is unknown. In evaluating cellular energetics and metabolism of t(11;14) and non-t(11;14) MM, we determine that venetoclax-sensitive myeloma has reduced mitochondrial respiration. Consistent with this, low electron transport chain (ETC) Complex I and Complex II activities correlate with venetoclax sensitivity. Inhibition of Complex I, using IACS-010759, an orally bioavailable Complex I inhibitor in clinical trials, as well as succinate ubiquinone reductase (SQR) activity of Complex II, using thenoyltrifluoroacetone (TTFA) or introduction of SDHC R72C mutant, independently sensitize resistant MM to venetoclax. We demonstrate that ETC inhibition increases BCL-2 dependence and the ‘primed’ state via the ATF4-BIM/NOXA axis. Further, SQR activity correlates with venetoclax sensitivity in patient samples irrespective of t(11;14) status. Use of SQR activity in a functional-biomarker informed manner may better select for MM patients responsive to venetoclax therapy. 1 Department of Hematology and Medical Oncology, Winship Cancer Institute, School of Medicine, Emory University, Atlanta, GA, USA. -
Supplementary Table 2: Infection-Sensitive Genes
Supplementary Table 2: Infection-Sensitive Genes Supplementary Table 2: Upregulated with Adenoviral Infection (pages 1 - 7)- genes that were significant by ANOVA as well as significantly increased in control compared to both 'infected control' (Ad-LacZ) and 'calcineurin infected' (Ad-aCaN). Downregulated with Adenoviral Infection (pages 7 - 13) as above except for direction of change. Columns: Probe Set- Affymetrix probe set identifier for RG-U34A microarray, Symbol and Title- annotated information for above probe set (annotation downloaded June, 2004), ANOVA- p-value for 1-way Analysis of Variance, Uninfected, Ad-LacZ and Ad- aCaN- mean ± SEM expression for uninfected control, adenovirus mediated LacZ treated control, and adenovirus mediated calcineurin treated cultures respectively. Upregulated with Adenoviral Infection Probe Set Symbol Title ANOVA Uninfected Ad-LacZ Ad-aCaN Z48444cds_at Adam10 a disintegrin and metalloprotease domain 10 0.00001 837 ± 31 1107 ± 24 1028 ± 29 L26986_at Adcy8 adenylyl cyclase 8 0.00028 146 ± 12 252 ± 21 272 ± 21 U94340_at Adprt ADP-ribosyltransferase 1 0.00695 2096 ± 100 2783 ± 177 2586 ± 118 U01914_at Akap8 A kinase anchor protein 8 0.00080 993 ± 44 1194 ± 65 1316 ± 44 AB008538_at Alcam activated leukocyte cell adhesion molecule 0.01012 2775 ± 136 3580 ± 216 3429 ± 155 M34176_s_at Ap2b1 adaptor-related protein complex 2, beta 1 subunit 0.01389 2408 ± 199 2947 ± 143 3071 ± 116 D44495_s_at Apex1 apurinic/apyrimidinic endonuclease 1 0.00089 4959 ± 185 5816 ± 202 6057 ± 158 U16245_at Aqp5 aquaporin 5 0.02710 -
Human Primitive Brain Displays Negative Mitochondrial-Nuclear Expression Correlation of Respiratory Genes
Downloaded from genome.cshlp.org on October 7, 2021 - Published by Cold Spring Harbor Laboratory Press Research Human primitive brain displays negative mitochondrial-nuclear expression correlation of respiratory genes Gilad Barshad, Amit Blumberg, Tal Cohen, and Dan Mishmar Department of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva 8410501, Israel Oxidative phosphorylation (OXPHOS), a fundamental energy source in all human tissues, requires interactions between mitochondrial (mtDNA)- and nuclear (nDNA)-encoded protein subunits. Although such interactions are fundamental to OXPHOS, bi-genomic coregulation is poorly understood. To address this question, we analyzed ∼8500 RNA-seq exper- iments from 48 human body sites. Despite well-known variation in mitochondrial activity, quantity, and morphology, we found overall positive mtDNA-nDNA OXPHOS genes’ co-expression across human tissues. Nevertheless, negative mtDNA- nDNA gene expression correlation was identified in the hypothalamus, basal ganglia, and amygdala (subcortical brain re- gions, collectively termed the “primitive” brain). Single-cell RNA-seq analysis of mouse and human brains revealed that this phenomenon is evolutionarily conserved, and both are influenced by brain cell types (involving excitatory/inhibitory neu- rons and nonneuronal cells) and by their spatial brain location. As the “primitive” brain is highly oxidative, we hypothesized that such negative mtDNA-nDNA co-expression likely controls for the high mtDNA transcript levels, which enforce tight OXPHOS regulation, rather than rewiring toward glycolysis. Accordingly, we found “primitive” brain-specific up-regula- tion of lactate dehydrogenase B (LDHB), which associates with high OXPHOS activity, at the expense of LDHA, which pro- motes glycolysis. Analyses of co-expression, DNase-seq, and ChIP-seq experiments revealed candidate RNA-binding proteins and CEBPB as the best regulatory candidates to explain these phenomena. -
Epigenetic Changes in Human Model KMT2A Leukemias Highlight Early Events During Leukemogenesis
Epigenetic changes in human model KMT2A leukemias highlight early events during leukemogenesis Thomas Milan1, Magalie Celton1, Karine Lagacé1, Élodie Roques1, Safia Safa-Tahar-Henni1, Eva Bresson2,3,4, Anne Bergeron2,3,4, Josée Hebert5,6, Soheil Meshinchi7, Sonia Cellot8, Frédéric Barabé2,3,4, 1,6 Brian T Wilhelm Author contributions: BTW and TM designed the study, analyzed data and drafted the manuscript. TM and KL performed ChIP-seq and ATAC-seq, analysed the data and generated figures. MC performed Methyl-seq experiments, analysed data, generated figures and drafted the manuscript. SS-T-H assisted with the ATAC-seq analysis and generation of figures. KL, ER, EB, and AB helped with molecular biology work, cloning and cell culture. EB, AB and FB generated the model on mice from CD34+ cells. SM provided expression and clinical data for patient samples and JH and SC collected, characterized, and banked the local patient samples used in this study. Affiliations: 1Laboratory for High Throughput Biology, Institute for Research in Immunology and Cancer, Montréal, QC, Canada 2Centre de recherche en infectiologie du CHUL, Centre de recherche du CHU de Québec – Université Laval, Québec City, QC, Canada, 3CHU de Québec – Université Laval – Hôpital Enfant-Jésus; Québec City, QC, Canada; 4Department of Medicine, Université Laval, Quebec City, QC, Canada 5Division of Hematology-Oncology and Leukemia Cell Bank of Quebec, Maisonneuve-Rosemont Hospital, Montréal, QC, Canada, 6Department of Medicine, Université de Montréal, Montréal, QC, Canada, 7Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA 8Department of pediatrics, division of Hematology, Ste-Justine Hospital, Montréal, QC, Canada Running head: Early epigenetic changes in KM3-AML *Correspondence to: Brian T Wilhelm Institute for Research in Immunology and Cancer Université de Montréal P.O.