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Disease Reference Book
The Counsyl Foresight™ Carrier Screen 180 Kimball Way | South San Francisco, CA 94080 www.counsyl.com | [email protected] | (888) COUNSYL The Counsyl Foresight Carrier Screen - Disease Reference Book 11-beta-hydroxylase-deficient Congenital Adrenal Hyperplasia .................................................................................................................................................................................... 8 21-hydroxylase-deficient Congenital Adrenal Hyperplasia ...........................................................................................................................................................................................10 6-pyruvoyl-tetrahydropterin Synthase Deficiency ..........................................................................................................................................................................................................12 ABCC8-related Hyperinsulinism........................................................................................................................................................................................................................................ 14 Adenosine Deaminase Deficiency .................................................................................................................................................................................................................................... 16 Alpha Thalassemia............................................................................................................................................................................................................................................................. -
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 -
Mitochondrial Protein Quality Control Mechanisms
G C A T T A C G G C A T genes Review Mitochondrial Protein Quality Control Mechanisms Pooja Jadiya * and Dhanendra Tomar * Center for Translational Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA * Correspondence: [email protected] (P.J.); [email protected] (D.T.); Tel.: +1-215-707-9144 (D.T.) Received: 29 April 2020; Accepted: 15 May 2020; Published: 18 May 2020 Abstract: Mitochondria serve as a hub for many cellular processes, including bioenergetics, metabolism, cellular signaling, redox balance, calcium homeostasis, and cell death. The mitochondrial proteome includes over a thousand proteins, encoded by both the mitochondrial and nuclear genomes. The majority (~99%) of proteins are nuclear encoded that are synthesized in the cytosol and subsequently imported into the mitochondria. Within the mitochondria, polypeptides fold and assemble into their native functional form. Mitochondria health and integrity depend on correct protein import, folding, and regulated turnover termed as mitochondrial protein quality control (MPQC). Failure to maintain these processes can cause mitochondrial dysfunction that leads to various pathophysiological outcomes and the commencement of diseases. Here, we summarize the current knowledge about the role of different MPQC regulatory systems such as mitochondrial chaperones, proteases, the ubiquitin-proteasome system, mitochondrial unfolded protein response, mitophagy, and mitochondria-derived vesicles in the maintenance of mitochondrial proteome and health. The proper understanding of mitochondrial protein quality control mechanisms will provide relevant insights to treat multiple human diseases. Keywords: mitochondria; proteome; ubiquitin; proteasome; chaperones; protease; mitophagy; mitochondrial protein quality control; mitochondria-associated degradation; mitochondrial unfolded protein response 1. Introduction Mitochondria are double membrane, dynamic, and semiautonomous organelles which have several critical cellular functions. -
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 -
Cldn19 Clic2 Clmp Cln3
NewbornDx™ Advanced Sequencing Evaluation When time to diagnosis matters, the NewbornDx™ Advanced Sequencing Evaluation from Athena Diagnostics delivers rapid, 5- to 7-day results on a targeted 1,722-genes. A2ML1 ALAD ATM CAV1 CLDN19 CTNS DOCK7 ETFB FOXC2 GLUL HOXC13 JAK3 AAAS ALAS2 ATP1A2 CBL CLIC2 CTRC DOCK8 ETFDH FOXE1 GLYCTK HOXD13 JUP AARS2 ALDH18A1 ATP1A3 CBS CLMP CTSA DOK7 ETHE1 FOXE3 GM2A HPD KANK1 AASS ALDH1A2 ATP2B3 CC2D2A CLN3 CTSD DOLK EVC FOXF1 GMPPA HPGD K ANSL1 ABAT ALDH3A2 ATP5A1 CCDC103 CLN5 CTSK DPAGT1 EVC2 FOXG1 GMPPB HPRT1 KAT6B ABCA12 ALDH4A1 ATP5E CCDC114 CLN6 CUBN DPM1 EXOC4 FOXH1 GNA11 HPSE2 KCNA2 ABCA3 ALDH5A1 ATP6AP2 CCDC151 CLN8 CUL4B DPM2 EXOSC3 FOXI1 GNAI3 HRAS KCNB1 ABCA4 ALDH7A1 ATP6V0A2 CCDC22 CLP1 CUL7 DPM3 EXPH5 FOXL2 GNAO1 HSD17B10 KCND2 ABCB11 ALDOA ATP6V1B1 CCDC39 CLPB CXCR4 DPP6 EYA1 FOXP1 GNAS HSD17B4 KCNE1 ABCB4 ALDOB ATP7A CCDC40 CLPP CYB5R3 DPYD EZH2 FOXP2 GNE HSD3B2 KCNE2 ABCB6 ALG1 ATP8A2 CCDC65 CNNM2 CYC1 DPYS F10 FOXP3 GNMT HSD3B7 KCNH2 ABCB7 ALG11 ATP8B1 CCDC78 CNTN1 CYP11B1 DRC1 F11 FOXRED1 GNPAT HSPD1 KCNH5 ABCC2 ALG12 ATPAF2 CCDC8 CNTNAP1 CYP11B2 DSC2 F13A1 FRAS1 GNPTAB HSPG2 KCNJ10 ABCC8 ALG13 ATR CCDC88C CNTNAP2 CYP17A1 DSG1 F13B FREM1 GNPTG HUWE1 KCNJ11 ABCC9 ALG14 ATRX CCND2 COA5 CYP1B1 DSP F2 FREM2 GNS HYDIN KCNJ13 ABCD3 ALG2 AUH CCNO COG1 CYP24A1 DST F5 FRMD7 GORAB HYLS1 KCNJ2 ABCD4 ALG3 B3GALNT2 CCS COG4 CYP26C1 DSTYK F7 FTCD GP1BA IBA57 KCNJ5 ABHD5 ALG6 B3GAT3 CCT5 COG5 CYP27A1 DTNA F8 FTO GP1BB ICK KCNJ8 ACAD8 ALG8 B3GLCT CD151 COG6 CYP27B1 DUOX2 F9 FUCA1 GP6 ICOS KCNK3 ACAD9 ALG9 -
Voyaging Around Clpb/Hsp100 Proteins and Plant Heat Tolerance
Published Online: 9 May 2019 Proc Indian Natn Sci Acad 85 No. 4 December 2019 pp. 791-802 Printed in India. DOI: 10.16943/ptinsa/2019/49592 Review Article Voyaging Around ClpB/Hsp100 Proteins and Plant Heat Tolerance RATNESH CHANDRA MISHRA* and ANIL GROVER Department of Plant Molecular Biology, University of Delhi South Campus, New Delhi 110 021, India (Received on 04 September 2018; Revised on 18 January 2019; Accepted on 27 February 2019) Temperature is one of the key physical parameters that fine tunes plant growth and development. However, above the optimal range, it can negatively affect the physiology of plants. Supraoptimal temperature brings incongruity in cellular proteostasis resulting in the build-up of insoluble toxic protein aggregates. To prevent protein misfolding and aggregation, cells deploy different strategies including synthesis of heat shock proteins (Hsp) belonging to different families, like small Hsps (sHsps), Hsp40, Hsp60, Hsp70. Once these aggregates are formed, their dissolution and recovery of the functional proteins occurs by the action of Caseinolytic Protease B (ClpB)/Hsp100, which are evolutionarily conserved in bacteria, fungi and plants. ClpB function during heat stress (HS) is important and appears indispensable, as mutant bacteria, yeast as well as plants lacking ClpB protein fail to survive HS. Genetic expression of ClpB proteins is modulated both by high temperature as well as developmental cues. Plant contains three isoforms of ClpB/Hsp100, one each localized to cytoplasm (ClpB-C), chloroplast (ClpB-P) and mitochondria (ClpB-M), against one in bacteria and two in yeast. Among these, ClpB- C protein in particular governs the thermotolerance response in plants. -
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. -
Gene Section Review
Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL INIST-CNRS Gene Section Review NDUFA13 (NADH:ubiquinone oxidoreductase subunit A13) Mafalda Pinto, Valdemar Máximo IPATIMUP Institute of Molecular Pathology and Immunology of the University of Porto, Portugal (MP, VM); I3S - Institute for Innovation and Helath Research, University of Porto, Portugal (MP, VM); Department of Pathology and Oncology, Medical Faculty of the University of Porto, Porto, Portugal (VM); [email protected]; [email protected] Published in Atlas Database: November 2015 Online updated version : http://AtlasGeneticsOncology.org/Genes/NDUFA13ID50482ch19p13.html Printable original version : http://documents.irevues.inist.fr/bitstream/handle/2042/66061/11-2015-NDUFA13ID50482ch19p13.pdf DOI: 10.4267/2042/66061 This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. © 2016 Atlas of Genetics and Cytogenetics in Oncology and Haematology Abstract Location: 19p13.11 (Chromosome 19: 19,626,545- 19,644,285 forward strand.) (Chidambaram et al., Short communication on NDUFA13, with data on 2000). DNA/RNA, on the protein encoded and where this Location (base pair) : Starts at 19515989 and ends gene is implicated. at 19528126 bp (according to COSMIC) Keywords Local order: Orientation: Forward Strand. Between NDUFA13; GRIM-19; mitochondria complex I; theGATAD2A and YJEFN3 genes. apoptosis. DNA/RNA Identity Note Other names: B16.6, CDA016, CGI-39, GRIM-19, NDUFA13 is a protein-coding gene, which encodes GRIM19, complex I B16.6 subunit a subunit of the mitochondrial respiratory chain HGNC (Hugo): NDUFA13 NADH dehydrogenase (Complex I). Atlas Genet Cytogenet Oncol Haematol. 2016; 20(8) 431 NDUFA13 (NADH:ubiquinone oxidoreductase subunit A13) Pinto M, Máximo V. -
Human CLPB) Is a Potent Mitochondrial Protein Disaggregase That Is Inactivated By
bioRxiv preprint doi: https://doi.org/10.1101/2020.01.17.911016; this version posted January 18, 2020. 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. Skd3 (human CLPB) is a potent mitochondrial protein disaggregase that is inactivated by 3-methylglutaconic aciduria-linked mutations Ryan R. Cupo1,2 and James Shorter1,2* 1Department of Biochemistry and Biophysics, 2Pharmacology Graduate Group, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, U.S.A. *Correspondence: [email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.01.17.911016; this version posted January 18, 2020. 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 Cells have evolved specialized protein disaggregases to reverse toxic protein aggregation and restore protein functionality. In nonmetazoan eukaryotes, the AAA+ disaggregase Hsp78 resolubilizes and reactivates proteins in mitochondria. Curiously, metazoa lack Hsp78. Hence, whether metazoan mitochondria reactivate aggregated proteins is unknown. Here, we establish that a mitochondrial AAA+ protein, Skd3 (human CLPB), couples ATP hydrolysis to protein disaggregation and reactivation. The Skd3 ankyrin-repeat domain combines with conserved AAA+ elements to enable stand-alone disaggregase activity. A mitochondrial inner-membrane protease, PARL, removes an autoinhibitory peptide from Skd3 to greatly enhance disaggregase activity. Indeed, PARL-activated Skd3 dissolves α-synuclein fibrils connected to Parkinson’s disease. Human cells lacking Skd3 exhibit reduced solubility of various mitochondrial proteins, including anti-apoptotic Hax1. -
Skd3 (Human CLPB) Is a Potent Mitochondrial Protein Disaggregase That Is Inactivated By
bioRxiv preprint first posted online Jan. 18, 2020; doi: http://dx.doi.org/10.1101/2020.01.17.911016. The copyright holder for this preprint (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Skd3 (human CLPB) is a potent mitochondrial protein disaggregase that is inactivated by 3-methylglutaconic aciduria-linked mutations Ryan R. Cupo1,2 and James Shorter1,2* 1Department of Biochemistry and Biophysics, 2Pharmacology Graduate Group, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, U.S.A. *Correspondence: [email protected] 1 bioRxiv preprint first posted online Jan. 18, 2020; doi: http://dx.doi.org/10.1101/2020.01.17.911016. The copyright holder for this preprint (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. ABSTRACT Cells have evolved specialized protein disaggregases to reverse toxic protein aggregation and restore protein functionality. In nonmetazoan eukaryotes, the AAA+ disaggregase Hsp78 resolubilizes and reactivates proteins in mitochondria. Curiously, metazoa lack Hsp78. Hence, whether metazoan mitochondria reactivate aggregated proteins is unknown. Here, we establish that a mitochondrial AAA+ protein, Skd3 (human CLPB), couples ATP hydrolysis to protein disaggregation and reactivation. The Skd3 ankyrin-repeat domain combines with conserved AAA+ elements to enable stand-alone disaggregase activity. A mitochondrial inner-membrane protease, PARL, removes an autoinhibitory peptide from Skd3 to greatly enhance disaggregase activity. Indeed, PARL-activated Skd3 dissolves α-synuclein fibrils connected to Parkinson’s disease. -
Neonatal Hemochromatosis: a Congenital Alloimmune Hepatitis
Reprinted with permission from Thieme Medical Publishers (Semin Liver Dis. 2007 Aug;27(3):243-250) Homepage at www.thieme.com Neonatal Hemochromatosis: A Congenital Alloimmune Hepatitis Peter F. Whitington, M.D.1 ABSTRACT Neonatal hemochromatosis (NH) is a rare and enigmatic disease that has been clinically defined as severe neonatal liver disease in association with extrahepatic siderosis. It recurs at an alarming rate in the offspring of certain women; the rate and pattern of recurrence led us to hypothesize that maternal alloimmunity is the likely cause at least of recurrent cases. This hypothesis led to a trial of gestational treatment to prevent the recurrence of severe NH, which has been highly successful adding strength to the alloimmune hypothesis. Laboratory proof of an alloimmune mechanism has been gained by reproducing the disease in a mouse model. NH should be suspected in any very sick newborn with evidence of liver disease and in cases of late intrauterine fetal demise. Given the pathology of the liver and the mechanism of liver injury, NH could best be classified as congenital alloimmune hepatitis. KEYWORDS: Neonatal hemochromatosis, acute liver failure, alloimmune disease, cirrhosis, hepatitis Neonatal hemochromatosis (NH) is clinically NH could best be classified as congenital alloimmune defined as severe neonatal liver disease in association hepatitis. with extrahepatic siderosis in a distribution similar to that seen in hereditary hemochromatosis.1–4 Consider- able evidence indicates that it is a gestational disease in ETIOLOGY AND PATHOGENESIS which fetal liver injury is the dominant feature. Because The name hemochromatosis implies that iron is involved of the abnormal accumulation of iron in liver and other in the pathogenesis of NH. -
GRACILE Syndrome, a Lethal Metabolic Disorder with Iron
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Am. J. Hum. Genet. 71:863–876, 2002 GRACILE Syndrome, a Lethal Metabolic Disorder with Iron Overload, Is Caused by a Point Mutation in BCS1L Ilona Visapa¨a¨,1,3 Vineta Fellman,7 Jouni Vesa,1 Ayan Dasvarma,8 Jenna L. Hutton,2 Vijay Kumar,5 Gregory S. Payne,2 Marja Makarow,5 Rudy Van Coster,9 Robert W. Taylor,10 Douglass M. Turnbull,10 Anu Suomalainen,6 and Leena Peltonen1,3,4 Departments of 1Human Genetics and 2Biological Chemistry, University of California Los Angeles School of Medicine, Los Angeles; 3Department of Molecular Medicine, National Public Health Institute, 4Department of Medical Genetics, 5Institute of Biotechnology, and 6Department of Neurology and Programme of Neurosciences, University of Helsinki, and 7Hospital for Children and Adolescents, Helsinki University Central Hospital, Helsinki; 8Murdoch Children’s Research Institute, Melbourne, Australia; 9Department of Pediatrics, Ghent University Hospital, Ghent, Belgium; and 10Department of Neurology, University of Newcastle upon Tyne, Newcastle, United Kingdom GRACILE (growth retardation, aminoaciduria, cholestasis, iron overload, lactacidosis, and early death) syndrome is a recessively inherited lethal disease characterized by fetal growth retardation, lactic acidosis, aminoaciduria, cholestasis, and abnormalities in iron metabolism. We previously localized the causative gene to a 1.5-cM region on chromosome 2q33-37. In the present study, we report the molecular defect causing this metabolic disorder, by identifying a homozygous missense mutation that results in an S78G amino acid change in the BCS1L gene in Finnish patients with GRACILE syndrome, as well as five different mutations in three British infants.