DOCSLIB.ORG

Clinical Implications of Mitochondrial Dysfunction Stanley Muravchick, M.D., Ph.D.,* Richard J

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Clinical Implications of Mitochondrial Dysfunction Stanley Muravchick, M.D., Ph.D.,* Richard J Ⅵ REVIEW ARTICLE David C. Warltier, M.D., Ph.D., Editor Anesthesiology 2006; 105:819–37 Copyright © 2006, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc. Clinical Implications of Mitochondrial Dysfunction Stanley Muravchick, M.D., Ph.D.,* Richard J. Levy, M.D.† Mitochondria produce metabolic energy, serve as biosensors phosphorylation,1 a process conducted by a series of five for oxidative stress, and eventually become effector organelles enzyme complexes located on the inner mitochondrial Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/105/4/819/360218/0000542-200610000-00029.pdf by guest on 25 September 2021 for cell death through apoptosis. The extent to which these membrane (fig. 1). Four of these complexes comprise manifold mitochondrial functions are altered by previously unrecognized actions of anesthetic agents seems to explain and the mitochondrial electron transport chain (ETC) and link a wide variety of perioperative phenomena that are cur- function as a biochemical “conveyor belt” for electrons. rently of interest to anesthesiologists from both a clinical and a Oxidative phosphorylation couples the oxidation of re- scientific perspective. In addition, many surgical patients may duced nicotinamide adenine dinucleotide and flavin ad- be at increased perioperative risk because of inherited or ac- enine dinucleotide, generated by the Krebs cycle and by quired mitochondrial dysfunction leading to increased oxida- ␤ tive stress. This review summarizes the essential aspects of the the -oxidation of fatty acids, to the phosphorylation of bioenergetic process, presents current knowledge regarding adenosine diphosphate (ADP) to adenosine triphosphate the effects of anesthetics on mitochondrial function and the (ATP). Electron donation to complex I (reduced nicotin- extent to which mitochondrial state determines anesthetic re- amide adenine dinucleotide–ubiquinone oxidoreduc- quirement and potential anesthetic toxicity, and considers some of the many implications that our knowledge of mito- tase) initiates this process. Alternatively, electrons orig- chondrial dysfunction poses for anesthetic management and inating from succinate and from reduced flavin adenine perioperative medicine. dinucleotide can be channeled into the ETC through complex II (succinate–ubiquinone oxidoreductase). MITOCHONDRIA not only generate and modulate bioen- Electrons are transported from complex I or II to com- ergy but also serve as the final effectors for the termina- plex III (ubiquinone–cytochrome c oxidoreductase) via tion of cell viability as organisms approach the end of a mobile electron carrier, coenzyme Q (ubiquinone), their lifespan. Therefore, the implications of these pro- and subsequently on to complex IV (cytochrome c oxi- cesses with regard to understanding evolution, disease, dase) via cytochrome c. Complex IV uses electrons from aging, and death are profound. Particularly relevant to cytochrome c to reduce molecular oxygen, the final anesthesiologists is the role of mitochondria in determin- acceptor of electrons, to water at that site. ing the response of the nervous system to anesthetic Intrinsically linked to this process of electron transport agents, in initiating mechanisms of cell injury or protec- is the generation and maintenance of a hydrogen ion tion after ischemic, hypoxic, or toxic injuries, and their gradient across the inner mitochondrial membrane. The ability to precipitate critical illness in individuals with inner membrane separates the intermembrane space inherited or acquired mitochondrial disorders. These from the mitochondrial matrix. The gradient is estab- aspects of mitochondrial biology and pathophysiology lished by proton pumps in ETC complexes I, III, and IV. will be briefly summarized in this clinically oriented The F1F0–ATPase (ATP synthase) complex within the review. inner membrane uses this proton motive force to phos- phorylate ADP. This last step in the overall process of The Bioenergetic Process oxidative phosphorylation produces the ATP that serves as the fundamental “currency” needed for most energy- Mitochondria produce the energy needed for normal requiring biologic transactions. Another membrane-inte- cellular function and metabolic homeostasis by oxidative grated protein, adenine nucleotide translocase, regulates an “antiport” process that moves ADP and ATP in oppo- * Professor of Anesthesiology and Critical Care, Hospital of the University of site directions across the inner mitochondrial mem- Pennsylvania. † Assistant Professor of Anesthesiology and Pediatrics, Depart- ment of Anesthesiology and Critical Care Medicine, Division of Cardiothoracic brane. Adenine nucleotide translocase delivers ATP to Anesthesiology, The Children’s Hospital of Philadelphia. energy-requiring sites, mostly in the cytosol, and simul- Received from the Department of Anesthesiology and Critical Care, University taneously resupplies the ATP synthase complex with of Pennsylvania School of Medicine, and the Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania. Submitted for publication July 15, 2005. Accepted for new substrate. publication June 20, 2006. Support was provided solely from institutional and/or The hydrogen ion gradient established by the process departmental sources. Address correspondence to Dr. Muravchick: Department of Anesthesiology and of oxidative phosphorylation can also be dissipated by Critical Care, Dulles Suite 680, Hospital of the University of Pennsylvania, 3400 proton leakage back into the matrix through the inner Spruce Street, Philadelphia, Pennsylvania 19104-4283. [email protected]. Individual article reprints may be purchased through the Journal Web site, www. membrane that bypasses the ATP synthase complex. anesthesiology.org. Uncoupling proteins (UCPs) within the inner membrane Anesthesiology, V 105, No 4, Oct 2006 819 820 S. MURAVCHICK AND R. J. LEVY Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/105/4/819/360218/0000542-200610000-00029.pdf by guest on 25 September 2021 Fig. 1. Schematic representation of the mitochondrial components needed for oxidative phosphorylation. Complexes I–IV, located within the inner mitochondrial membrane, are oxidase complexes that, along with coenzyme Q (Co Q) and cytochrome c (Cyto C), comprise the electron transport chain. Dotted lines indicate pathway for electron flow. Complexes I, III, and IV also pump hydrogen ions (dashed lines) into the intermembrane space and generate the electrochemical gradient that ultimately powers the phosphor- ylation of adenosine diphosphate (ADP) to adenosine triphosphate (ATP) by ATP synthase. Inner membrane–bound uncoupling protein (UCP) is an alternate return path for hydrogen ions. Adenine nucleotide translocase (ANT) regulates the balance of ATP and ؍ ؍ ؍ ADP within the mitochondrial matrix. FADH2 flavin adenine dinucleotide; H2O water; NAD nicotinamide adenine dinucle- ؍ ؍ ؍ otide; NADH reduced nicotinamide adenine dinucleotide; O2 oxygen; Pi inorganic phosphate. Copyright © 2000 American Diabetes Association. Modified with permission from The American Diabetes Association, from Boss et al.4 provide this alternate pathway for proton influx. In ef- subunits needed for electron transport and oxidative fect, UCPs convert some of the electrochemical energy phosphorylation, although the majority of mitochondrial generated by the ETC into heat rather than into ATP. The proteins needed for normal bioenergetic function are rate of proton leakage through a UCP seems to be influ- encoded by nuclear DNA (nDNA)7 and therefore must enced by a variety of conditions, including changes in be imported into the mitochondrial matrix from the cell the magnitude of the hydrogen ion gradient itself, in- cytosol.8 Complex IV of the ETC, for example, contains creased catecholamines levels, and variations in fatty 13 subunits, 10 of which are encoded in nDNA. The acid concentrations.2 UCP-1, also called thermogenin, expression of the mitochondrial genome itself requires a was originally characterized in the mitochondria of single mitochondrial transcription factor that arises from brown fat cells3 and is now known to play a role in the nuclear genome.9 nonshivering thermogenesis in human neonates. Subse- Overall, the human mitochondrial genome encodes for quently, additional UCP isoforms were identified in a 13 peptides (subunits of complexes I, III, and IV and the 4 variety of tissues. Although their precise metabolic ATP synthase complex), 2 ribosomal ribonucleic acids functions have yet to be determined, UCPs may play an (RNAs), and 22 transfer RNAs. Nuclear DNA encodes for 5 important role in adult obesity, diabetes mellitus, and at least 1,000 proteins that are needed for mitochondrial perhaps other conditions where the regulation of oxida- bioenergetic and metabolic functions and for mtDNA tive metabolism seems to be disrupted. expression and replication.10 Although there may be as many as 1,000 copies of mtDNA in most cells, acquired mtDNA point mutations and base pair deletions are ex- Mitochondrial Biogenesis tremely rare and are normally found in only a minute proportion of total mtDNA11 despite the fact that The mitochondrion, unique among mammalian or- mtDNA, unlike nDNA, lacks histone protection and is ganelles, contains multiple copies of a small circular surrounded by potentially damaging oxidative influenc- genome of approximately 16,000 nucleotide base pairs. es.12 This observation supports the hypothesis that there This mitochondrial DNA (mtDNA)
Load more

Recommended publications
  • P'sfi. DEJITJ1
    \ She Visits the P'S fi. DEJITJ1 Cuhaq Patriots MESSENGER, J. Li .iii at the Risk Mr. Maloney's of Jler Life. Lugubrious Jiorrors of the Occupation. Cabanos Prisoq ANNOUNCED TWENTY Where Hebel DEATPS IN A DAY. Leaders /Ire Shot. The City's Dismissed Death Havana, March 18..I looked from my Jierald Explains JIoW window this morning before the sun had risen. Pb Performed Jiis Across the bay the grimly beautiful Duties. towers of Castle Morro were outlined against the sky, a mass of exquisite color, The city has until recently employed a gray, white and yellow, the crimson and man known as the death messenger. The of from the high¬ office Is vacant just now for reasons which gold flag Spain floating have been made widely public, but it will est turret. Almost beneath my window a have to be filled again. sentry slouched along, his rifle across his But for the Investigation into the affairs arm. i of Bellevue Hospital few people would ^' have known that there existed so Suddenly, with a splendor which dazzled pic¬ turesquely named an official in this prosaic my eyes, the sun burst into view, turning city. The lord keeper of the great seal has the water to gold and touching the castle not a more dignified title than the death walls with the glory of flame. messenger, and certainly he has a much less one. If will consider the Just across the water, came the terrifying you then, matter you will perceive that there could sound of six rifle shots. The sounds were not be a more awful occupation than that slightly muffled, as though coming through of death messenger.
    [Show full text]
  • Human-Touch-2015.Pdf
    The Human Touch Volume 8 u 2015 THE JOURNAL OF POETRY, PROSE, AND VISUAL ART University of Colorado u Anschutz Medical Campus FRONT COVER artwork April 2010 #5, March 2013 #1, October 2011 #4, from the series Deterioration | DAISY PATTON Digital media BACK COVER artwork Act of Peace | JAMES ENGELN Color digital photograph University of Colorado Anschutz Medical Campus The Human Touch Volume 8 u 2015 Layout & Printing The Human Touch Volume 8 u 2015 Volume 8 u 2015 BOOK LAYOUT / DESIGN EDITORS IN CHIEF: db2 Design Deborah Beebe (art director/principal) Romany Redman 303.898.0345 :: [email protected] Rachel Foster Rivard www.db2design.com Helena Winston PRINTING Light-Speed Color EDITORIAL BOARD: Bill Daley :: 970.622.9600 [email protected] Amanda Brooke Ryan D’Souza This journal and all of its contents with no exceptions are covered under the Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 Anjali Dhurandhar License. To view a summary of this license, please see Lynne Fox http://creativecommons.org/licenses/by-nc-nd/3.0/us/. To review the license in Leslie Palacios-Helgeson full, please see http://creativecommons.org/licenses/by-nc-nd/3.0/us/legalcode. Fair use and other rights are not affected by this license. Amisha Singh To learn more about this and other Creative Commons licenses, please see http://creativecommons.org/about/licenses/meet-the-licenses. SUPERVISING EDITORS: * To honor the creative expression of the journal’s contributors, the unique and deliberate formats of their work have been preserved. Henry N. Claman Therese Jones © All Authors/Artists Hold Their Own Copyright 2 3 University of Colorado Anschutz Medical Campus The Human Touch Volume 8 u 2015 Contents VOUME 8 u 2015 Preface ............................................................................................................
    [Show full text]
  • The Patriarchal Devaluation of the Irish Goddess, the Mor-Rioghan Kelley Flannery Rowan Florida International University, [email protected]
    Florida International University FIU Digital Commons FIU Electronic Theses and Dissertations University Graduate School 1-19-2005 Monstrum in femine figura : the patriarchal devaluation of the Irish goddess, the Mor-rioghan Kelley Flannery Rowan Florida International University, [email protected] DOI: 10.25148/etd.FI14030210 Follow this and additional works at: https://digitalcommons.fiu.edu/etd Part of the Religion Commons Recommended Citation Rowan, Kelley Flannery, "Monstrum in femine figura : the patriarchal devaluation of the Irish goddess, the Mor-rioghan" (2005). FIU Electronic Theses and Dissertations. 1058. https://digitalcommons.fiu.edu/etd/1058 This work is brought to you for free and open access by the University Graduate School at FIU Digital Commons. It has been accepted for inclusion in FIU Electronic Theses and Dissertations by an authorized administrator of FIU Digital Commons. For more information, please contact [email protected]. FLORIDA INTERNATIONAL UNIVERSITY Miami, Florida MONSTRUM IN FEMINE FIGURA: THE PATRIARCHAL DEVALUATION OF THE IRISH GODDESS, THE MOR-RIOGHAN A thesis submitted in partial fulfillment of the requirements for the degree of MASTER OF ARTS in RELIGIOUS STUDIES by Kelley Flannery Rowan 2005 To: Dean R. Bruce Dunlap College of Arts and Sciences This thesis, written by Kelley Flannery Rowan, and entitled Monstrum in Femine Figura: The Patriarchal Devaluation of the Irish Goddess, The Mor-rioghan, having been approved in respect to style and intellectual content, is referred to you for judgment. We have read this thesis and recommend that it be approved. Lesley Northup Erik Larson Christine Gudorf ajor Professor Date of Defense: January 19, 2005 The thesis of Kelley Flannery Rowan is approved.
    [Show full text]
  • Keening the Dead: Ancient History Or a Ritual for Today?
    Article Keening the Dead: Ancient History or a Ritual for Today? Mary Mc Laughlin Irish World Academy of Music and Dance, University of Limerick, Limerick, V94 T9PX, Ireland; [email protected] Received: 6 March 2019; Accepted: 24 March 2019; Published: 29 March 2019 Abstract: In his 1909 work ‘Rites De Passage’, Arnold van Gennep acknowledges that a ritual often contains ‘rites within rites’. So, it was with the ancient ritual of the Irish wake, at the center of which was another ritual, that of the keen, the Irish funeral lament. The past tense is used tentatively here, as in this article the author explores the resilience of the ritual and how, rather than becoming extinct, the keen seems to spend periods of time underground before erupting again in a new form, attuning itself to a more contemporaneous social situation. Drawing on ethnographic and bibliographic research undertaken between 2010 and 2018, the author traces some of the history of the keen within the ritual of the Irish wake and funeral and gives instances of how it is being reconfigured in the 21st century. This continuation of the ritual, albeit in a new format, seems to speak to a deep emotional and spiritual need that may not be satisfied by more conventional religion in Ireland. Finally, the author considers the keen’s relevance and place in Irish society today. Keywords: keen; wake; funeral; Ireland; tradition; custom; culture; history; chant 1. Introduction Arnold van Gennep theorized that rituals often contain rites within other rites (van Gennep 1909, p. 23). This insight is highly relevant to the subject of this essay, which examines the ancient Irish funeral lament known as the keen, within its traditional context of the greater ritual of the Irish wake.
    [Show full text]
  • Siva's Demon Devotee
    1 The Place of Kåraikkål Ammaiyår in South Indian History Kåraikkål Ammaiyår’s poetry bridges the classical Tamil world and the devotional milieu in which Sanskritic myths are localized in a Tamil landscape and infused with Tamil modes of relating to the divine. Although Ammaiyår does not directly praise the Tamil land or Tamil language as the later Íaiva poets do, her poetry is animated by literary and cultural elements that are defi ning features of the classical Tamil world. Ammaiyår makes reference to many of Íiva’s heroic deeds as related in Sanskrit myths and epics, but she is espe- cially devoted to Íiva dancing in the cremation ground, a scenario that resonates profoundly with Tamil ideas of death and dessicated wastelands. In order to understand how Ammaiyår’s poetry situates Íiva in the Tamil landscape, in this chapter I present a brief historical overview of the milieu in which Kåraikkål Ammaiyår composed her poetry, including the literary traditions that inform her work. A vivid portrait of life in Tamilnadu in the early centuries of the Common Era emerges from the earliest surviving Tamil literature, which was likely composed or compiled between the fi rst century BCE and the fi fth century CE. Literature can convey certain social and cultural facts, but since it “refracts as much as it refl ects,” it is neces- sary to “enter the realm of the symbolic values that writers express through the ‘facts’ and ‘objective entities’” (Ramanujan 1999a, 52). In classical Tamil literature human behavior and natural landscape are key components of a poetic system that refl ects and structures the values and aesthetics of the Tamil world during the centuries leading up to the beginnings of devotional Hinduism.
    [Show full text]
  • Home Is Where the Heart Is? : Identity and Belonging in Asian American Literature
    Home Is Where the Heart Is? Identity and Belonging in Asian American Literature Inaugural-Dissertation zur Erlangung des Grades eines Doktor der Philosophie in der Fakultät für Philologie der Ruhr-Universität Bochum vorgelegt von Heike Berner Gedruckt mit der Genehmigung der Fakultät für Philologie der Ruhr-Universität Bochum Referent: Prof. Dr. David Galloway Koreferent: Prof. Dr. Gerd Stratmann Tag der mündlichen Prüfung: 15. Januar 2003 Danksagungen Für die Unterstützung, die ich beim Schreiben dieser Arbeit erhalten habe, möchte ich hier stellvertretend einigen Menschen danken: Jungja und Gerd Berner, Christian Jungck, Bob und Diana Lee, Sharlyn M. Rhee, Elaine H. Kim, Steven Lee und Ruth Desmond, Yong Soon Min, Kyungmi Shin, Young Chung, Jean Shin, Rocío Davis, Josh Kavaloski und Jamie Lee, David Galloway und Gerd Stratmann und meinen Freundinnen und Freunden und Kolleginnen und Kollegen. 4 Contents I. Introduction 6 A. Identities 10 B. Mistaken Identities 15 II. Discourses on Identity in Asian America 19 A. Aiiieeeee! 19 B. The Big Aiiieeeee! 24 C. Other Points of View 25 D. 'Got Rice?' – Asian American Studies Then and Now 35 III. Identity and Belonging in Asian American Classics 43 A. "Asian American Classics" 43 1. John Okada: No-No Boy 44 a) Historical Background 44 b) Short Summary 48 c) Identity Conflict 49 d) Finding an Identity 51 2. Louis Chu: Eat a Bowl of Tea 61 a) Historical Background 62 b) Short Summary 63 c) Identity Conflict 64 d) Solution 67 3. Okada, Chu, and the Aiiieeeee!-editors: Asian American Realism 68 B. Maxine Hong Kingston: Of Women Warriors and China Men 71 1.
    [Show full text]
  • The Encyclopedia of Suicide, 2Nd Revised Edition (Facts on File
    THE ENCYCLOPEDIA OF SUICIDE Second Edition THE ENCYCLOPEDIA OF SUICIDE Second Edition Glen Evans Norman L. Farberow, Ph.D. Kennedy Associates Foreword by Alan L. Berman, Ph.D. Executive Director, American Association of Suicidology The Encyclopedia of Suicide, Second Edition Copyright © 2003 by Margaret M. Evans All rights reserved. No part of this book may be reproduced or utilized in any form or by any means, elec- tronic or mechanical, including photocopying, recording, or by any information storage or retrieval sys- tems, without permission in writing from the publisher. For information contact: Facts On File, Inc. 132 West 31st Street New York NY 10001 Library of Congress Cataloging-in-Publication Data Evans, Glen The encyclopedia of suicide / Glen Evans, Norman L. Farberow.—2nd ed. p. cm. Includes bibliographical references and index. ISBN 0-8160-4525-9 1. Suicide—Dictionaries. 2. Suicide—United States—Dictionaries. 3. Suicide—United States—Statistics. 4. Suicide victims—Services for—United States—Directories. 5. Suicide victims—Services for— Canada—Directories. I. Farberow, Norman L. II. Title. III. Series. HV6545 .E87 2003 362.28'03—dc21 2002027166 Facts On File books are available at special discounts when purchased in bulk quantities for businesses, associations, institutions, or sales promotions. Please call our Special Sales Department in New York at (212) 967-8800 or (800) 322-8755. You can find Facts On File on the World Wide Web at http://www.factsonfile.com Text and cover design by Cathy Rincon Printed in the United States of America VB FOF 10 9 8 7 6 5 4 3 2 1 This book is printed on acid-free paper.
    [Show full text]
  • The Canterbury Tales
    The Canterbury Tales by Geoffrey Chaucer All new material ©2008 Enotes.com Inc. or its Licensors. All Rights Reserved. No portion may be reproduced without permission in writing from the publisher. For complete copyright information please see the online version of this text at http://www.enotes.com/canterbury Table of Contents Introduction.........................................................................................................................................................1 Overview..............................................................................................................................................................2 Geoffrey Chaucer Biography.............................................................................................................................8 Summary............................................................................................................................................................10 Summary and Analysis.....................................................................................................................................15 1: General Prologue Summary and Analysis.........................................................................................15 2: The Knight's Tale Summary and Analysis........................................................................................20 3: The Miller's Tale Summary and Analysis.........................................................................................23 4: The Reeve's Tale Summary
    [Show full text]
  • Open Letter from Kjeldor of Hallwyll Call From
    edition 51 - year 18 a.t.d. H Call from Methraton Thul Last summer we liberated a city they bring to this city. We need passes through them as a guest or and won a capital for Mitraspera the support of the Seals and the as a new resident. and a new mistress. But a title free cities so that we can plan I already know now that she and the recognition as such is not the future of our capital together. will be happy about every new enough for a capital to fulfil its Use this opportunity, because life - because Methraton Thul purpose. only those who speak can be feels what is happening within So I, Dohreah MacDermott, First heard. Methraton Thul should her walls, she feels the joy, the Typhe of the New Age, call grow strong and according to courage and the zest for action upon you to help your capital our wishes and needs, become a that she brings. and make it flourish. We need celebration, but also a home and building materials, goods, food a place of safe exchange. Signed and of course craftsmen, workers The gates of Methraton Thul are Typhe Dohreah and traders and the knowledge open to every settler, whether he Open letter from Kjeldor of Hallwyll First Reading at the Synod of Pi- to think about this time and the as an archon is over. It is not the oneers time to come, about myself, about time for an archon who focuses on what lies ahead, about this world the one or the making of peace.
    [Show full text]
  • Religion, Medicine, Bioethics, and the Law in End-Of-Life Care: South Asian Religious Adherent Perspectives
    Religion, Medicine, Bioethics, and the Law in End-of-life Care: South Asian Religious Adherent Perspectives by Sean Hillman A thesis submitted in conformity with the requirements for the degree of Doctor of Philosophy Graduate Departments of Department for the Study of Religion, Joint Centre for Bioethics, Centre for South Asian Studies University of Toronto © Copyright by Sean Hillman (2019) Religion, Medicine, Bioethics, and the Law in End-of-life Care: South Asian Religious Adherent Perspectives (2019) Sean Hillman Department for the Study of Religion, Joint Centre for Bioethics, Centre for South Asian Studies University of Toronto ABSTRACT This study investigates end-of-life care issues in contemporary India from the perspectives of Indian and Tibetan religious adherents, through the lenses of religious studies, bioethics and the law. The need comes from a paucity in bioethics studies related to the ancient Indic religious traditions of Buddhism, Hinduism and Jainism, and from some studies ignoring the non-theistic Indic traditions altogether. Additionally, direct requests came from a Jain community organization for bioethical approaches to an end-of-life ritual fasting and immobilization practice (sallekhanā) as it continues to be legally contested. Medical approaches to decision-making can assist with the dual purposes of protecting vulnerable Jains from coercion and also in satisfying detractors. A major research question was whether religious views impact end-of-life decision- making of patients, families and health care professionals. Although specifically answered in the final chapter, medical decision-making pervades the conversations and analysis throughout, and it is proposed that decision-making moments that involve patients and/or families along with health care providers create micro-level transient neocultures, stemming from Ortiz’s transculturation theory.
    [Show full text]
  • Animals and the Irish Mouth in Edna O'brien's Fiction
    Journal of Ecocriticism 5(2) July 2013 Animals and the Irish Mouth in Edna O’Brien’s Fiction Maureen O’Connor, University College Cork1 Abstract From Edna O’Brien’s earliest novels, many commentators have noted that desire is at the core of the narratives. The true irony in such observations lies in their frequently blinkered understanding of what comprises that desire, reducing it to a heteronormative, Barbara-Cartland-style pursuit of “romance.” While the characters themselves may think this is what they hunger for, the text inevitably opens up vaster sources of insatiable longing. As Mary Douglas has established, “the body is capable of furnishing a natural system of symbols” (xxxii), and in O’Brien’s texts the human mouth, especially when at its most “animal,” metonymizes numerous desires, most often balked and even impossible ones, including those that actuate the scene of writing. Mouths are everywhere in O’Brien’s novels, licking, yawning, weeping, swallowing, keening, grimacing, biting, shrieking, chewing, singing, speaking, and opening in silence. These mouths give voice to the immaterial, and even animate the inorganic, which, for all of its immateriality, can yet resist manipulation. The inscrutable “inhuman” voice that emerges ultimately reveals “that words themselves are sphinxes, hybrids of the animal, the human, and the inorganic” (Ellmann 77). The natural cries of all animals, even of those animals with whom we have not been acquainted, never fail to make themselves sufficiently understood; this cannot be said of language. Edmund Burke The absolutely foreign alone can instruct us Emmanuel Levinas Ireland is the most rich, inescapable land.
    [Show full text]
  • In Vain I Chant a Magic Verseby
    IN VAIN I CHANT A MAGIC VERSEBY by Danielle Harms A Thesis Submitted to the Graduate Faculty of George Mason University in Partial Fulfillment of The Requirements for the Degree of Master of Fine Arts Creative Writing Committee: Director Department Chairperson Dean, College of Humanities and Social Sciences Date: Aped Spring Semester 2014 George Mason University Fairfax, VA In Vain I Chant A Magic Verse A Thesis submitted in partial fulfillment of the requirements for the degree of Name of Degree, as in Master or Doctor of Science or Philosophy at George Mason University by Danielle Harms Bachelor of Arts Gustavus Adolphus College, 2009 Director: Kyoko Mori, Professor Department of English for Master of Fine Arts Spring Semester 2014 George Mason University Fairfax, VA This work is licensed under a creative commons attribution-noderivs 3.0 unported license. ii DEDICATION This is dedicated to my endlessly encouraging partner Greg and the many faculty, friends, and family who mentored me as I pursued this project. And above all, this work is dedicated to those who survived staggering adversity yet still found the fortitude to share their stories. iii ACKNOWLEDGEMENTS I would like to thank those who helped me along the way, especially my thesis advisor, Kyoko Mori. iv TABLE OF CONTENTS Page Abstract .............................................................................................................................. vi To Tell a Truth: An Introduction .......................................................................................
    [Show full text]