Mitochondrial Carriers Regulating Insulin Secretion Profiled in Human Islets Upon Metabolic Stress
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![RT² Profiler PCR Array (96-Well Format and 384-Well [4 X 96] Format)](https://docslib.b-cdn.net/cover/1030/rt%C2%B2-profiler-pcr-array-96-well-format-and-384-well-4-x-96-format-301030.webp)
RT² Profiler PCR Array (96-Well Format and 384-Well [4 X 96] Format)
RT² Profiler PCR Array (96-Well Format and 384-Well [4 x 96] Format) Human Mitochondria Cat. no. 330231 PAHS-087ZA For pathway expression analysis Format For use with the following real-time cyclers RT² Profiler PCR Array, Applied Biosystems® models 5700, 7000, 7300, 7500, Format A 7700, 7900HT, ViiA™ 7 (96-well block); Bio-Rad® models iCycler®, iQ™5, MyiQ™, MyiQ2; Bio-Rad/MJ Research Chromo4™; Eppendorf® Mastercycler® ep realplex models 2, 2s, 4, 4s; Stratagene® models Mx3005P®, Mx3000P®; Takara TP-800 RT² Profiler PCR Array, Applied Biosystems models 7500 (Fast block), 7900HT (Fast Format C block), StepOnePlus™, ViiA 7 (Fast block) RT² Profiler PCR Array, Bio-Rad CFX96™; Bio-Rad/MJ Research models DNA Format D Engine Opticon®, DNA Engine Opticon 2; Stratagene Mx4000® RT² Profiler PCR Array, Applied Biosystems models 7900HT (384-well block), ViiA 7 Format E (384-well block); Bio-Rad CFX384™ RT² Profiler PCR Array, Roche® LightCycler® 480 (96-well block) Format F RT² Profiler PCR Array, Roche LightCycler 480 (384-well block) Format G RT² Profiler PCR Array, Fluidigm® BioMark™ Format H Sample & Assay Technologies Description The Human Mitochondria RT² Profiler PCR Array profiles the expression of 84 genes involved in the biogenesis and function of the cell's powerhouse organelle. The genes monitored by this array include regulators and mediators of mitochondrial molecular transport of not only the metabolites needed for the electron transport chain and oxidative phosphorylation, but also the ions required for maintaining the mitochondrial membrane polarization and potential important for ATP synthesis. Metabolism and energy production are not the only functions of mitochondria. -
Identification of P.A684V Missense Mutation in the WFS1 Gene As a Frequent Cause of Autosomal Dominant Optic Atrophy and Hearing
RESEARCH ARTICLE Identification of p.A684V Missense Mutation in the WFS1 Gene as a Frequent Cause of Autosomal Dominant Optic Atrophy and Hearing Impairment Nanna D. Rendtorff,1 Marianne Lodahl,1 Houda Boulahbel,2 Ida R. Johansen,1 Arti Pandya,3 Katherine O. Welch,4 Virginia W. Norris,4 Kathleen S. Arnos,4 Maria Bitner-Glindzicz,5 Sarah B. Emery,6 Marilyn B. Mets,7 Toril Fagerheim,8 Kristina Eriksson,9 Lars Hansen,1 Helene Bruhn,10 Claes M€oller,11 Sture Lindholm,12 Stefan Ensgaard,13 Marci M. Lesperance,6 and Lisbeth Tranebjaerg1,14*,† 1Wilhelm Johannsen Centre for Functional Genome Research, Department of Cellular and Molecular Medicine (ICMM), The Panum Institute, University of Copenhagen, Copenhagen, Denmark 2Biotech Research & Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark 3Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia 4Department of Biology, Gallaudet University, Washington DC 5UCL Institute of Child Health, London, UK 6Division of Pediatric Otolaryngology, Department of Otolaryngology-Head and Neck Surgery, UniversityofMichiganHealthSystem,AnnArbor,Michigan 7Departments of Ophthalmology and Surgery, Feinberg School of Medicine, Northwestern University, Evanston, Illinois 8Division of Child and Adolescent Health, Department of Medical Genetics, University Hospital of North Norway, Tromsø, Norway 9Department of Ophthalmology, Lundby Hospital, Gothenburg, Sweden 10Division of Metabolic Diseases, Department of Laboratory Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden 11Department of Audiology/Disability Research (SIDR), O¨rebro University, Sweden 12Department of Audiology, County Hospital, Kalmar, Sweden 13Department of Psychiatrics, Stockholm, Sweden 14Department of Audiology, Bispebjerg Hospital, Copenhagen, Denmark Received 19 July 2010; Accepted 2 February 2011 Optic atrophy (OA) and sensorineural hearing loss (SNHL) are these additional eight families. -
Dominant Optic Atrophy
Lenaers et al. Orphanet Journal of Rare Diseases 2012, 7:46 http://www.ojrd.com/content/7/1/46 REVIEW Open Access Dominant optic atrophy Guy Lenaers1*, Christian Hamel1,2, Cécile Delettre1, Patrizia Amati-Bonneau3,4,5, Vincent Procaccio3,4,5, Dominique Bonneau3,4,5, Pascal Reynier3,4,5 and Dan Milea3,4,5,6 Abstract Definition of the disease: Dominant Optic Atrophy (DOA) is a neuro-ophthalmic condition characterized by a bilateral degeneration of the optic nerves, causing insidious visual loss, typically starting during the first decade of life. The disease affects primary the retinal ganglion cells (RGC) and their axons forming the optic nerve, which transfer the visual information from the photoreceptors to the lateral geniculus in the brain. Epidemiology: The prevalence of the disease varies from 1/10000 in Denmark due to a founder effect, to 1/30000 in the rest of the world. Clinical description: DOA patients usually suffer of moderate visual loss, associated with central or paracentral visual field deficits and color vision defects. The severity of the disease is highly variable, the visual acuity ranging from normal to legal blindness. The ophthalmic examination discloses on fundoscopy isolated optic disc pallor or atrophy, related to the RGC death. About 20% of DOA patients harbour extraocular multi-systemic features, including neurosensory hearing loss, or less commonly chronic progressive external ophthalmoplegia, myopathy, peripheral neuropathy, multiple sclerosis-like illness, spastic paraplegia or cataracts. Aetiology: Two genes (OPA1, OPA3) encoding inner mitochondrial membrane proteins and three loci (OPA4, OPA5, OPA8) are currently known for DOA. Additional loci and genes (OPA2, OPA6 and OPA7) are responsible for X-linked or recessive optic atrophy. -
TIMM8A Gene Translocase of Inner Mitochondrial Membrane 8A
TIMM8A gene translocase of inner mitochondrial membrane 8A Normal Function The TIMM8A gene provides instructions for making a protein that is found inside mitochondria, which are structures within cells that convert the energy from food into a form that cells can use. Mitochondria have two membranes, an outer membrane and an inner membrane, which are separated by a fluid-filled area called the intermembrane space. The TIMM8A protein is found in the intermembrane space, where it forms a complex (a group of proteins that work together) with a very similar protein called TIMM13. This complex transports other proteins across the intermembrane space to the mitochondrial inner membrane. Health Conditions Related to Genetic Changes Deafness-dystonia-optic neuronopathy syndrome At least 20 mutations in the TIMM8A gene have been found to cause deafness-dystonia- optic neuronopathy (DDON) syndrome. Most of these mutations result in the absence of functional TIMM8A protein inside the mitochondria, which prevents the formation of the TIMM8A/TIMM13 complex. Researchers believe that the lack of this complex leads to abnormal transport of proteins across the intermembrane space, although it is unclear how abnormal protein transport affects the function of the mitochondria and causes the signs and symptoms of DDON syndrome. Some people with DDON syndrome have large DNA deletions that remove the entire TIMM8A gene and one end of a neighboring gene known as BTK. Mutations in the BTK gene cause X-linked agammaglobulinemia (XLA), which is characterized by an increased susceptibility to infections. Individuals with large DNA deletions that include the TIMM8A gene and the BTK gene have the signs and symptoms of both DDON syndrome and XLA. -
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 -
Deafness-Dystonia-Optic Neuronopathy Syndrome
Deafness-dystonia-optic neuronopathy syndrome Description Deafness-dystonia-optic neuronopathy (DDON) syndrome, also known as Mohr- Tranebjærg syndrome, is characterized by hearing loss that begins early in life, problems with movement, impaired vision, and behavior problems. This condition occurs almost exclusively in males. The first symptom of DDON syndrome is hearing loss caused by nerve damage in the inner ear (sensorineural hearing loss), which begins in early childhood. The hearing impairment worsens over time, and most affected individuals have profound hearing loss by age 10. People with DDON syndrome typically begin to develop problems with movement during their teens, although the onset of these symptoms varies among affected individuals. Some people experience involuntary tensing of the muscles (dystonia), while others have difficulty coordinating movements (ataxia). The problems with movement usually worsen over time. Individuals with DDON syndrome have normal vision during childhood, but they may develop vision problems due to breakdown of the nerves that carry information from the eyes to the brain (optic atrophy). Affected individuals can develop an increased sensitivity to light (photophobia) or other vision problems beginning in adolescence. Their sharpness of vision (visual acuity) slowly worsens, often leading to legal blindness in mid-adulthood. People with this condition may also have behavior problems, including changes in personality and aggressive or paranoid behaviors. They also usually develop a gradual decline in thinking and reasoning abilities (dementia) in their forties. The lifespan of individuals with DDON syndrome depends on the severity of the disorder. People with severe cases have survived into their teenage years, while those with milder cases have lived into their sixties. -
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. -
Role and Regulation of the P53-Homolog P73 in the Transformation of Normal Human Fibroblasts
Role and regulation of the p53-homolog p73 in the transformation of normal human fibroblasts Dissertation zur Erlangung des naturwissenschaftlichen Doktorgrades der Bayerischen Julius-Maximilians-Universität Würzburg vorgelegt von Lars Hofmann aus Aschaffenburg Würzburg 2007 Eingereicht am Mitglieder der Promotionskommission: Vorsitzender: Prof. Dr. Dr. Martin J. Müller Gutachter: Prof. Dr. Michael P. Schön Gutachter : Prof. Dr. Georg Krohne Tag des Promotionskolloquiums: Doktorurkunde ausgehändigt am Erklärung Hiermit erkläre ich, dass ich die vorliegende Arbeit selbständig angefertigt und keine anderen als die angegebenen Hilfsmittel und Quellen verwendet habe. Diese Arbeit wurde weder in gleicher noch in ähnlicher Form in einem anderen Prüfungsverfahren vorgelegt. Ich habe früher, außer den mit dem Zulassungsgesuch urkundlichen Graden, keine weiteren akademischen Grade erworben und zu erwerben gesucht. Würzburg, Lars Hofmann Content SUMMARY ................................................................................................................ IV ZUSAMMENFASSUNG ............................................................................................. V 1. INTRODUCTION ................................................................................................. 1 1.1. Molecular basics of cancer .......................................................................................... 1 1.2. Early research on tumorigenesis ................................................................................. 3 1.3. Developing -
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. -
Comprehensive Genomic Diagnosis of Non-Syndromic and Syndromic
Cabanillas et al. BMC Medical Genomics (2018) 11:58 https://doi.org/10.1186/s12920-018-0375-5 RESEARCH ARTICLE Open Access Comprehensive genomic diagnosis of non- syndromic and syndromic hereditary hearing loss in Spanish patients Rubén Cabanillas1*†, Marta Diñeiro1†, Guadalupe A. Cifuentes1, David Castillo2, Patricia C. Pruneda2, Rebeca Álvarez1, Noelia Sánchez-Durán1, Raquel Capín1, Ana Plasencia3, Mónica Viejo-Díaz3, Noelia García-González3, Inés Hernando3, José L. Llorente3, Alfredo Repáraz-Andrade4, Cristina Torreira-Banzas4, Jordi Rosell5, Nancy Govea5, Justo Ramón Gómez-Martínez3, Faustino Núñez-Batalla3, José A. Garrote6, Ángel Mazón-Gutiérrez7, María Costales3,7, María Isidoro-García8, Belén García-Berrocal8, Gonzalo R. Ordóñez2 and Juan Cadiñanos1* Abstract Background: Sensorineural hearing loss (SNHL) is the most common sensory impairment. Comprehensive next-generation sequencing (NGS) has become the standard for the etiological diagnosis of early-onset SNHL. However, accurate selection of target genomic regions (gene panel/exome/genome), analytical performance and variant interpretation remain relevant difficulties for its clinical implementation. Methods: We developed a novel NGS panel with 199 genes associated with non-syndromic and/or syndromic SNHL. We evaluated the analytical sensitivity and specificity of the panel on 1624 known single nucleotide variants (SNVs) and indels on a mixture of genomic DNA from 10 previously characterized lymphoblastoid cell lines, and analyzed 50 Spanish patients with presumed hereditary SNHL -
![RT² Profiler PCR Array (96-Well Format and 384-Well [4 X 96] Format)](https://docslib.b-cdn.net/cover/1423/rt%C2%B2-profiler-pcr-array-96-well-format-and-384-well-4-x-96-format-2611423.webp)
RT² Profiler PCR Array (96-Well Format and 384-Well [4 X 96] Format)
RT² Profiler PCR Array (96-Well Format and 384-Well [4 x 96] Format) Rat Mitochondria Cat. no. 330231 PARN-087ZA For pathway expression analysis Format For use with the following real-time cyclers RT² Profiler PCR Array, Applied Biosystems® models 5700, 7000, 7300, 7500, Format A 7700, 7900HT, ViiA™ 7 (96-well block); Bio-Rad® models iCycler®, iQ™5, MyiQ™, MyiQ2; Bio-Rad/MJ Research Chromo4™; Eppendorf® Mastercycler® ep realplex models 2, 2s, 4, 4s; Stratagene® models Mx3005P®, Mx3000P®; Takara TP-800 RT² Profiler PCR Array, Applied Biosystems models 7500 (Fast block), 7900HT (Fast Format C block), StepOnePlus™, ViiA 7 (Fast block) RT² Profiler PCR Array, Bio-Rad CFX96™; Bio-Rad/MJ Research models DNA Format D Engine Opticon®, DNA Engine Opticon 2; Stratagene Mx4000® RT² Profiler PCR Array, Applied Biosystems models 7900HT (384-well block), ViiA 7 Format E (384-well block); Bio-Rad CFX384™ RT² Profiler PCR Array, Roche® LightCycler® 480 (96-well block) Format F RT² Profiler PCR Array, Roche LightCycler 480 (384-well block) Format G RT² Profiler PCR Array, Fluidigm® BioMark™ Format H Sample & Assay Technologies Description The Rat Mitochondria RT² Profiler PCR Array profiles the expression of 84 genes involved in the biogenesis and function of the cell's powerhouse organelle. The genes monitored by this array include regulators and mediators of mitochondrial molecular transport of not only the metabolites needed for the electron transport chain and oxidative phosphorylation, but also the ions required for maintaining the mitochondrial membrane polarization and potential important for ATP synthesis. Metabolism and energy production are not the only functions of mitochondria. -
Protein Tyrosine Phosphorylation in Haematopoietic Cancers and the Functional Significance of Phospho- Lyn SH2 Domain
Protein Tyrosine Phosphorylation in Haematopoietic Cancers and the Functional Significance of Phospho- Lyn SH2 Domain By Lily Li Jin A thesis submitted in conformity with the requirements for the degree of Ph.D. in Molecular Genetics, Graduate Department of Molecular Genetics, in the University of Toronto © Copyright by Lily Li Jin (2015) Protein Tyrosine Phosphorylation in Haematopoietic Cancers and the Functional Significance of Phospho-Lyn SH2 Domain Lily Li Jin 2015 Ph.D. in Molecular Genetics Graduate Department of Molecular Genetics University of Toronto Abstract Protein-tyrosine phosphorylation (pY) is a minor but important protein post-translational modification that modulates a wide range of cellular functions and is involved in cancer. Dysregulation of tyrosine kinases (TKs) and protein-tyrosine phosphatases (PTPs) have been observed in multiple myeloma (MM) and acute myeloid leukemia (AML) and is a subject of study. Using recently developed mass spectrometry-based proteomics techniques, quantitative PTP expression and cellular pY profiles were generated for MM cell lines and mouse xenograft tumors, as well as primary AML samples. Integrated comprehensive analyses on these data implicated a subset of TKs and PTPs in MM and AML, with valuable insights gained on the dynamic regulation of pY in biological systems. In particular, I propose a model that describes the cellular pY state as a functional output of the total activated TKs and PTPs in the cell. My results show that the global pY profile in the cancer models is quantitatively related to the cellular levels of activated TKs and PTPs. Furthermore, the identity of the implicated TK/PTPs is system- ii dependent, demonstrating context-dependent regulation of pY.