Autophagy - Autophagy
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Autophagic Digestion of Leishmania Major by Host Macrophages Is
Frank et al. Parasites & Vectors (2015) 8:404 DOI 10.1186/s13071-015-0974-3 RESEARCH Open Access Autophagic digestion of Leishmania major by host macrophages is associated with differential expression of BNIP3, CTSE, and the miRNAs miR-101c, miR-129, and miR-210 Benjamin Frank1, Ana Marcu1, Antonio Luis de Oliveira Almeida Petersen2,3, Heike Weber4, Christian Stigloher5, Jeremy C. Mottram2, Claus Juergen Scholz4 and Uta Schurigt1* Abstract Background: Autophagy participates in innate immunity by eliminating intracellular pathogens. Consequently, numerous microorganisms have developed strategies to impair the autophagic machinery in phagocytes. In the current study, interactions between Leishmania major (L. m.) and the autophagic machinery of bone marrow-derived macrophages (BMDM) were analyzed. Methods: BMDM were generated from BALB/c mice, and the cells were infected with L. m. promastigotes. Transmission electron microscopy (TEM) and electron tomography were used to investigate the ultrastructure of BMDM and the intracellular parasites. Affymetrix® chip analyses were conducted to identify autophagy-related messenger RNAs (mRNAs) and microRNAs (miRNAs). The protein expression levels of autophagy related 5 (ATG5), BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), cathepsin E (CTSE), mechanistic target of rapamycin (MTOR), microtubule-associated proteins 1A/1B light chain 3B (LC3B), and ubiquitin (UB) were investigated through western blot analyses. BMDM were transfected with specific small interfering RNAs (siRNAs) against autophagy-related genes and with mimics or inhibitors of autophagy-associated miRNAs. The infection rates of BMDM were determined by light microscopy after a parasite-specific staining. Results: The experiments demonstrated autophagy induction in BMDM after in vitro infection with L. -
Mitochondrial Micrornas in Aging and Neurodegenerative Diseases
cells Review Mitochondrial MicroRNAs in Aging and Neurodegenerative Diseases Albin John 1, Aaron Kubosumi 1 and P. Hemachandra Reddy 1,2,3,4,5,* 1 Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; [email protected] (A.J.); [email protected] (A.K.) 2 Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA 3 Department of Neurology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA 4 Department of Public Health, Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA 5 Department of Speech, Language, and Hearing Sciences, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA * Correspondence: [email protected]; Tel.: +1-806-743-3194 Received: 7 April 2020; Accepted: 27 May 2020; Published: 28 May 2020 Abstract: MicroRNAs (miRNAs) are important regulators of several biological processes, such as cell growth, cell proliferation, embryonic development, tissue differentiation, and apoptosis. Currently, over 2000 mammalian miRNAs have been reported to regulate these biological processes. A subset of microRNAs was found to be localized to human mitochondria (mitomiRs). Through years of research, over 400 mitomiRs have been shown to modulate the translational activity of the mitochondrial genome. While miRNAs have been studied for years, the function of mitomiRs and their role in neurodegenerative pathologies is not known. The purpose of our article is to highlight recent findings that relate mitomiRs to neurodegenerative diseases, including Alzheimer’s, Parkinson’s, and Huntington’s. We also discuss the involvement of mitomiRs in regulating the mitochondrial genome in age-related neurodegenerative diseases. -
Research Article Label-Free Proteomics of the Fetal Pancreas Identifies Deficits in the Peroxisome in Rats with Intrauterine Growth Restriction
Hindawi Oxidative Medicine and Cellular Longevity Volume 2019, Article ID 1520753, 15 pages https://doi.org/10.1155/2019/1520753 Research Article Label-Free Proteomics of the Fetal Pancreas Identifies Deficits in the Peroxisome in Rats with Intrauterine Growth Restriction Xiaomei Liu ,1 Yanyan Guo ,1 Jun Wang ,1,2 Linlin Gao ,3 and Caixia Liu 1 1Key Laboratory of Maternal-Fetal Medicine of Liaoning Province, Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, China 2Department of Obstetrics and Gynecology, Benxi Central Hospital of China Medical University, Benxi 117022, China 3Medical Research Center, Shengjing Hospital, China Medical University, Shenyang 110004, China Correspondence should be addressed to Xiaomei Liu; [email protected] Received 14 May 2019; Revised 31 August 2019; Accepted 9 September 2019; Published 3 November 2019 Guest Editor: Roberta Cascella Copyright © 2019 Xiaomei Liu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Aim. The objective of the present study was to identify differentially expressed proteins (DEPs) in the pancreas of a fetus with intrauterine growth restriction (IUGR) and to investigate the molecular mechanisms leading to adulthood diabetes in IUGR. Methods. The IUGR rat model was induced by maternal protein malnutrition. The fetal pancreas was collected at embryonic day 20 (E20). Protein was extracted, pooled, and subjected to label-free quantitative proteomic analysis. Bioinformatics analysis (GO and IPA) was performed to define the pathways and networks associated with DEPs. LC-MS results were confirmed by western blotting and/or quantitative PCR (q-PCR). -
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 -
Multiple Pathways for Protein Transport to Peroxisomes
Review Multiple Pathways for Protein Transport to Peroxisomes P.K. Kim 1,2 and E.H. Hettema 3 1 - Program in Cell Biology, Hospital for Sick Children, Toronto, ON, Canada M5G 1X8 2 - Department of Biochemistry, University of Toronto, Toronto, ON, Canada M5S 1A8 3 - Department of Molecular Biology and Biotechnology, University of Sheffield, Firth Court, Western Bank, Sheffield, South Yorkshire S10 2TN, United Kingdom Correspondence to E.H. Hettema: [email protected] http://dx.doi.org/10.1016/j.jmb.2015.02.005 Edited by S. High Abstract Peroxisomes are unique among the organelles of the endomembrane system. Unlike other organelles that derive most if not all of their proteins from the ER (endoplasmic reticulum), peroxisomes contain dedicated machineries for import of matrix proteins and insertion of membrane proteins. However, peroxisomes are also able to import a subset of their membrane proteins from the ER. One aspect of peroxisome biology that has remained ill defined is the role the various import pathways play in peroxisome maintenance. In this review, we discuss the available data on matrix and membrane protein import into peroxisomes. © 2015 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Introduction dependent on consumption of energy in the form of ATP. Several aspects of peroxisomal protein transport Peroxisomes are organelles found in almost all distinguish it from other translocation systems. For eukaryotic cells. They are bounded by a single example, peroxisomal proteins can fold, acquire membrane and are usually spherical. -
Global Ubiquitylation Analysis of Mitochondria in Primary Neurons
bioRxiv preprint doi: https://doi.org/10.1101/2021.04.01.438131; this version posted April 1, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. Global ubiquitylation analysis of mitochondria in primary neurons identifies physiological Parkin targets following activation of PINK1 Odetta Antico1#, Alban Ordureau2#, Michael Stevens1, Francois Singh1, Marek φ Gierlinski3, Erica Barini1 , Mollie L. Rickwood1, Alan Prescott4, Rachel Toth1, Ian G. Ganley1, J. Wade Harper2*, and Miratul M. K. Muqit1* 1MRC Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee, United Kingdom, DD1 5EH, U.K. 2Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA 3Data Analysis Group, Division of Computational Biology, School of Life Sciences, University of Dundee, Dundee, United Kingdom, DD1 5EH, U.K. 4Dundee Imaging Facility, School of Life Sciences, University of Dundee, Dundee, United Kingdom, DD1 5EH, U.K #Denotes Equal Contribution φCurrent address: AbbVie Deutschland GmbH & Co, Knollstr, 67061, Ludwigshafen, Germany *Correspondence: [email protected] or [email protected] Keywords Neurons, PINK1, Parkin, ubiquitin, Parkinson’s disease, Mitochondria, Running Title: Ubiquitin analysis of mitochondria in neurons 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.04.01.438131; this version posted April 1, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. -
Perkinelmer Genomics to Request the Saliva Swab Collection Kit for Patients That Cannot Provide a Blood Sample As Whole Blood Is the Preferred Sample
Zellweger Spectrum Disorder Panel Test Code D4611 Test Summary This panel analyzes 15 genes that have been associated with Zellweger Spectrum Disorders. Turn-Around-Time (TAT)* 3 - 5 weeks Acceptable Sample Types Whole Blood (EDTA) (Preferred sample type) DNA, Isolated Dried Blood Spots Saliva Acceptable Billing Types Self (patient) Payment Institutional Billing Commercial Insurance Indications for Testing This panel may be appropriate for individuals with signs and symptoms of a peroxisomal biogenesis disfuction and/or Zellweger syndrome spectrum disorder and/or a family history of these conditions. Test Description This panel analyzes 15 genes that have been associated with Zellweger Spectrum Disorders. Both sequencing and deletion/duplication (CNV) analysis will be performed on the coding regions of all genes included (unless otherwise marked). All analysis is performed utilizing Next Generation Sequencing (NGS) technology. CNV analysis is designed to detect the majority of deletions and duplications of three exons or greater in size. Smaller CNV events may also be detected and reported, but additional follow-up testing is recommended if a smaller CNV is suspected. All variants are classified according to ACMG guidelines. Condition Description Zellweger syndrome spectrum disorders include Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD), an intermediate form and infantile Refsum disease (IRD). Symptoms may include hypotonia, feeding problems, hearing and vision loss, seizures, distinctive facial characteristics and skeletal abnormalities. Zellweger spectrum disorder is estimated to occur in 1/50,000 individuals. Genes ACOX1, AMACR, HSD17B4, PEX1, PEX10, PEX12, PEX13, PEX14, PEX16, PEX19, PEX2, PEX26, PEX3, PEX5, PEX6 Test Methods and Limitations Sequencing is performed on genomic DNA using an Agilent targeted sequence capture method to enrich for the genes on this panel. -
FUNDC1 Sirna (M): Sc-145273
SANTA CRUZ BIOTECHNOLOGY, INC. FUNDC1 siRNA (m): sc-145273 BACKGROUND STORAGE AND RESUSPENSION FUNDC1 (FUN14 domain-containing protein 1) is a 155 amino acid protein Store lyophilized siRNA duplex at -20° C with desiccant. Stable for at least belonging to the FUN14 family. The gene encoding FUNDC1 maps to human one year from the date of shipment. Once resuspended, store at -20° C, chromosome Xp11.3 and mouse chromosome X A1.2. The X and Y chromo- avoid contact with RNAses and repeated freeze thaw cycles. somes are the human sex chromosomes. Chromosome X consists of about Resuspend lyophilized siRNA duplex in 330 µl of the RNAse-free water 153 million base pairs and nearly 1,000 genes. The combination of an X and provided. Resuspension of the siRNA duplex in 330 µl of RNAse-free water Y chromosome lead to normal male development while two copies of X lead makes a 10 µM solution in a 10 µM Tris-HCl, pH 8.0, 20 mM NaCl, 1 mM to normal female development. More than one copy of the X chromosome EDTA buffered solution. with a Y chromosome causes Klinefelter’s syndrome. A single copy of X alone leads to Turner’s syndrome. More than two copies of the X chromosome, APPLICATIONS in the absence of a Y chromosome, is known as Triple X syndrome. Color blindness, hemophilia, and Duchenne muscular dystrophy are well known X FUNDC1 siRNA (m) is recommended for the inhibition of FUNDC1 expression chromosome-linked conditions which affect males more frequently as males in mouse cells. -
Ceapins Block the Unfolded Protein Response Sensor Atf6a by Inducing a Neomorphic Inter-Organelle Tether
RESEARCH ARTICLE Ceapins block the unfolded protein response sensor ATF6a by inducing a neomorphic inter-organelle tether Sandra Elizabeth Torres1,2,3, Ciara M Gallagher2,3†‡, Lars Plate4,5†, Meghna Gupta2, Christina R Liem1,3, Xiaoyan Guo6,7, Ruilin Tian6,7, Robert M Stroud2, Martin Kampmann6,7, Jonathan S Weissman1,3*, Peter Walter2,3* 1Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States; 2Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States; 3Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, United States; 4Department of Chemistry, Vanderbilt University, Nashville, United States; 5Department of Biological Sciences, Vanderbilt University, Nashville, United States; 6Department of Biochemistry and Biophysics, Institute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, United States; 7Chan Zuckerberg Biohub, San Francisco, United States *For correspondence: [email protected] Abstract The unfolded protein response (UPR) detects and restores deficits in the endoplasmic (JSW); a [email protected] (PW) reticulum (ER) protein folding capacity. Ceapins specifically inhibit the UPR sensor ATF6 , an ER- tethered transcription factor, by retaining it at the ER through an unknown mechanism. Our † These authors contributed genome-wide CRISPR interference (CRISPRi) screen reveals that Ceapins function is completely equally to this work dependent on the ABCD3 peroxisomal transporter. Proteomics studies establish that ABCD3 Present address: ‡Cairn physically associates with ER-resident ATF6a in cells and in vitro in a Ceapin-dependent manner. Biosciences, San Francisco, Ceapins induce the neomorphic association of ER and peroxisomes by directly tethering the United States cytosolic domain of ATF6a to ABCD3’s transmembrane regions without inhibiting or depending on Competing interests: The ABCD3 transporter activity. -
S100A6 Is a Critical Regulator of Hematopoietic Stem Cells
Leukemia (2020) 34:3323–3337 https://doi.org/10.1038/s41375-020-0901-2 ARTICLE Normal hematopoiesis S100A6 is a critical regulator of hematopoietic stem cells 1 2 3 1 2 Tan Hooi Min Grahn ● Abhishek Niroula ● Ákos Végvári ● Leal Oburoglu ● Maroulio Pertesi ● 1 4 1 5 1 1 Sarah Warsi ● Fatemeh Safi ● Natsumi Miharada ● Sandra C. Garcia ● Kavitha Siva ● Yang Liu ● 6 2 3 1 Emma Rörby ● Björn Nilsson ● Roman A. Zubarev ● Stefan Karlsson Received: 12 February 2020 / Revised: 26 May 2020 / Accepted: 29 May 2020 / Published online: 19 June 2020 © The Author(s) 2020. This article is published with open access Abstract The fate options of hematopoietic stem cells (HSCs) include self-renewal, differentiation, migration, and apoptosis. HSCs self-renewal divisions in stem cells are required for rapid regeneration during tissue damage and stress, but how precisely intracellular calcium signals are regulated to maintain fate options in normal hematopoiesis is unclear. S100A6 knockout (KO) HSCs have reduced total cell numbers in the HSC compartment, decreased myeloid output, and increased apoptotic HSC numbers in steady state. S100A6KO HSCs had impaired self-renewal and regenerative capacity, not responding to 5- Fluorouracil. Our transcriptomic and proteomic profiling suggested that S100A6 is a critical HSC regulator. Intriguingly, S100A6KO HSCs showed decreased levels of phosphorylated Akt (p-Akt) and Hsp90, with an impairment of mitochondrial 1234567890();,: 1234567890();,: respiratory capacity and a reduction of mitochondrial calcium levels. We showed that S100A6 regulates intracellular and mitochondria calcium buffering of HSC upon cytokine stimulation and have demonstrated that Akt activator SC79 reverts the levels of intracellular and mitochondrial calcium in HSC. -
Downloaded Per Proteome Cohort Via the Web- Site Links of Table 1, Also Providing Information on the Deposited Spectral Datasets
www.nature.com/scientificreports OPEN Assessment of a complete and classifed platelet proteome from genome‑wide transcripts of human platelets and megakaryocytes covering platelet functions Jingnan Huang1,2*, Frauke Swieringa1,2,9, Fiorella A. Solari2,9, Isabella Provenzale1, Luigi Grassi3, Ilaria De Simone1, Constance C. F. M. J. Baaten1,4, Rachel Cavill5, Albert Sickmann2,6,7,9, Mattia Frontini3,8,9 & Johan W. M. Heemskerk1,9* Novel platelet and megakaryocyte transcriptome analysis allows prediction of the full or theoretical proteome of a representative human platelet. Here, we integrated the established platelet proteomes from six cohorts of healthy subjects, encompassing 5.2 k proteins, with two novel genome‑wide transcriptomes (57.8 k mRNAs). For 14.8 k protein‑coding transcripts, we assigned the proteins to 21 UniProt‑based classes, based on their preferential intracellular localization and presumed function. This classifed transcriptome‑proteome profle of platelets revealed: (i) Absence of 37.2 k genome‑ wide transcripts. (ii) High quantitative similarity of platelet and megakaryocyte transcriptomes (R = 0.75) for 14.8 k protein‑coding genes, but not for 3.8 k RNA genes or 1.9 k pseudogenes (R = 0.43–0.54), suggesting redistribution of mRNAs upon platelet shedding from megakaryocytes. (iii) Copy numbers of 3.5 k proteins that were restricted in size by the corresponding transcript levels (iv) Near complete coverage of identifed proteins in the relevant transcriptome (log2fpkm > 0.20) except for plasma‑derived secretory proteins, pointing to adhesion and uptake of such proteins. (v) Underrepresentation in the identifed proteome of nuclear‑related, membrane and signaling proteins, as well proteins with low‑level transcripts. -
The Role of Peroxisomes in Chronic Obstructive Pulmonary Disease
The Role of Peroxisomes in Chronic Obstructive Pulmonary Disease Inaugural Dissertation Submitted to the Faculty of Medicine in partial fulfilment of the requirements for the PhD-Degree of the Faculties of Veterinary Medicine and Medicine of the Justus Liebig University Giessen by Natalia El-Merhie of Minsk, Belarus Giessen 2016 From the Institute for Anatomy and Cell Biology, Division of Medical Cell Biology Director/Chairperson: Prof. Dr. Eveline Baumgart-Vogt of the Faculty of Medicine of Justus Liebig University Giessen First Supervisor and Committee Member: Prof. Dr. Eveline Baumgart-Vogt Second Supervisor and Committee Member: Prof. Christiane Herden Committee Members: Prof. Dr. Norbert Weissmann Date of Doctoral Defense: July 24, 2017 Declaration “I declare that I have completed this dissertation single-handedly without the unauthorized help of a second party and only with the assistance acknowledged therein. I have appropriately acknowledged and referenced all text passages that are derived literally from or are based on the content of published or unpublished work of others, and all information that relates to verbal communications. I have abided by the principles of good scientific conduct laid down in the charter of the Justus Liebig University of Giessen in carrying out the investigations described in the dissertation.” Giessen, December 15, 2016 Natalia El-Merhie List of Abbreviations α1AT, Alpha-1-antitrypsin AECI, Alveolar type I cells AECII, Alveolar type II cells APS, Ammonium persulfate ARE, Antioxidant response element