Mitochondrial dysfunctions in leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL)

Several inherited human diseases have been linked to mitochondrial aminoacyl-tRNA synthetases (mtARSs). Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a leukodystrophy caused by mutations in the DARS2 gene which encodes mitochondrial aspartyl-tRNA synt...

Full description

Saved in:
Bibliographic Details
Published inPloS one Vol. 14; no. 10; p. e0224173
Main Authors Lin, Tsu-Kung, Chang, Yung-Yee, Lin, Hung-Yu, Liou, Chia-Wei, Wang, Pei-Wen, Chuang, Jiin-Haur, Chen, Shang-Der, Chuang, Yao-Chung, Huang, Sheng-Teng, Hsu, Te-Yao, Peng, Cheng-Huei, Lan, Min-Yu
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 31.10.2019
Public Library of Science (PLoS)
Subjects
Aminoacyl-tRNA synthetases
Aspartate-tRNA ligase
Aspartate-tRNA Ligase - deficiency
Aspartate-tRNA Ligase - genetics
Base Sequence
Bioenergetics
Biology and Life Sciences
Biosynthesis
Brain stem
Chains
Deoxyribonucleic acid
Disease
DNA
EDTA
Electron transport
Elongation
Fibroblasts
Fibroblasts - pathology
Gene mutation
Genes
Genetic aspects
Hospitals
Humans
Lactates
Lactic acid
Leukodystrophy
Leukoencephalopathies - genetics
Leukoencephalopathies - pathology
Leukoencephalopathy
Ligases
Maintenance
Medical schools
Medicine
Medicine and Health Sciences
Mitochondria
Mitochondria - pathology
Mitochondrial diseases
Mitochondrial Diseases - genetics
Mitochondrial Diseases - pathology
Mitochondrial DNA
Morphology
Mutation
Neurology
Oxidative stress
Oxygen
Oxygen consumption
Pediatrics
Physiology
Proteins
RNA
Spinal cord
Transfer RNA
Translations
tRNA
United States > US
Taiwan
Online AccessGet full text
ISSN1932-6203
1932-6203
DOI10.1371/journal.pone.0224173

Cover

Abstract Several inherited human diseases have been linked to mitochondrial aminoacyl-tRNA synthetases (mtARSs). Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a leukodystrophy caused by mutations in the DARS2 gene which encodes mitochondrial aspartyl-tRNA synthetase. As mitochondrial ARSs are key components of the mitochondrial translation apparatus, we investigated the effects of DARS2 mutations on mitochondrial functions and mitochondrial morphology in an LBSL patient. In fibroblasts from the patient with LBSL, biosynthesis of respiratory chain complex proteins encoded by mitochondrial DNA was decreased, while those encoded by nuclear DNA were not. Cellular oxygen consumption rates and respiratory control ratio were decreased in the LBSL patient; in addition, fragmentation of mitochondria was increased, while their tubular elongation and interconnectivity were decreased. Taken together, these findings suggest that DARS2 mutations impair translations of mitochondrial DNA-encoded respiratory chain complex proteins, consequently causing dysfunction of cellular respiration and impediment of mitochondrial dynamics, which highlights the role of mtARSs in the maintenance of normal mitochondrial bioenergetics and dynamics.
AbstractList Several inherited human diseases have been linked to mitochondrial aminoacyl-tRNA synthetases (mtARSs). Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a leukodystrophy caused by mutations in the DARS2 gene which encodes mitochondrial aspartyl-tRNA synthetase. As mitochondrial ARSs are key components of the mitochondrial translation apparatus, we investigated the effects of DARS2 mutations on mitochondrial functions and mitochondrial morphology in an LBSL patient. In fibroblasts from the patient with LBSL, biosynthesis of respiratory chain complex proteins encoded by mitochondrial DNA was decreased, while those encoded by nuclear DNA were not. Cellular oxygen consumption rates and respiratory control ratio were decreased in the LBSL patient; in addition, fragmentation of mitochondria was increased, while their tubular elongation and interconnectivity were decreased. Taken together, these findings suggest that DARS2 mutations impair translations of mitochondrial DNA-encoded respiratory chain complex proteins, consequently causing dysfunction of cellular respiration and impediment of mitochondrial dynamics, which highlights the role of mtARSs in the maintenance of normal mitochondrial bioenergetics and dynamics.
Several inherited human diseases have been linked to mitochondrial aminoacyl-tRNA synthetases (mtARSs). Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a leukodystrophy caused by mutations in the DARS2 gene which encodes mitochondrial aspartyl-tRNA synthetase. As mitochondrial ARSs are key components of the mitochondrial translation apparatus, we investigated the effects of DARS2 mutations on mitochondrial functions and mitochondrial morphology in an LBSL patient. In fibroblasts from the patient with LBSL, biosynthesis of respiratory chain complex proteins encoded by mitochondrial DNA was decreased, while those encoded by nuclear DNA were not. Cellular oxygen consumption rates and respiratory control ratio were decreased in the LBSL patient; in addition, fragmentation of mitochondria was increased, while their tubular elongation and interconnectivity were decreased. Taken together, these findings suggest that DARS2 mutations impair translations of mitochondrial DNA-encoded respiratory chain complex proteins, consequently causing dysfunction of cellular respiration and impediment of mitochondrial dynamics, which highlights the role of mtARSs in the maintenance of normal mitochondrial bioenergetics and dynamics.
Several inherited human diseases have been linked to mitochondrial aminoacyl-tRNA synthetases (mtARSs). Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a leukodystrophy caused by mutations in the DARS2 gene which encodes mitochondrial aspartyl-tRNA synthetase. As mitochondrial ARSs are key components of the mitochondrial translation apparatus, we investigated the effects of DARS2 mutations on mitochondrial functions and mitochondrial morphology in an LBSL patient. In fibroblasts from the patient with LBSL, biosynthesis of respiratory chain complex proteins encoded by mitochondrial DNA was decreased, while those encoded by nuclear DNA were not. Cellular oxygen consumption rates and respiratory control ratio were decreased in the LBSL patient; in addition, fragmentation of mitochondria was increased, while their tubular elongation and interconnectivity were decreased. Taken together, these findings suggest that DARS2 mutations impair translations of mitochondrial DNA-encoded respiratory chain complex proteins, consequently causing dysfunction of cellular respiration and impediment of mitochondrial dynamics, which highlights the role of mtARSs in the maintenance of normal mitochondrial bioenergetics and dynamics.Several inherited human diseases have been linked to mitochondrial aminoacyl-tRNA synthetases (mtARSs). Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a leukodystrophy caused by mutations in the DARS2 gene which encodes mitochondrial aspartyl-tRNA synthetase. As mitochondrial ARSs are key components of the mitochondrial translation apparatus, we investigated the effects of DARS2 mutations on mitochondrial functions and mitochondrial morphology in an LBSL patient. In fibroblasts from the patient with LBSL, biosynthesis of respiratory chain complex proteins encoded by mitochondrial DNA was decreased, while those encoded by nuclear DNA were not. Cellular oxygen consumption rates and respiratory control ratio were decreased in the LBSL patient; in addition, fragmentation of mitochondria was increased, while their tubular elongation and interconnectivity were decreased. Taken together, these findings suggest that DARS2 mutations impair translations of mitochondrial DNA-encoded respiratory chain complex proteins, consequently causing dysfunction of cellular respiration and impediment of mitochondrial dynamics, which highlights the role of mtARSs in the maintenance of normal mitochondrial bioenergetics and dynamics.
Audience Academic
Author Chang, Yung-Yee
Chen, Shang-Der
Huang, Sheng-Teng
Chuang, Yao-Chung
Peng, Cheng-Huei
Lin, Tsu-Kung
Hsu, Te-Yao
Lin, Hung-Yu
Wang, Pei-Wen
Liou, Chia-Wei
Chuang, Jiin-Haur
Lan, Min-Yu
AuthorAffiliation University College London, UNITED KINGDOM
3 Department of Pediatric Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
2 Center for Parkinson’s Disease, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
1 Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
4 Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
5 Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan
6 Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
AuthorAffiliation_xml – name: 1 Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
– name: University College London, UNITED KINGDOM
– name: 4 Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
– name: 5 Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan
– name: 2 Center for Parkinson’s Disease, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
– name: 3 Department of Pediatric Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
– name: 6 Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
Author_xml – sequence: 1
  givenname: Tsu-Kung
  surname: Lin
  fullname: Lin, Tsu-Kung
– sequence: 2
  givenname: Yung-Yee
  surname: Chang
  fullname: Chang, Yung-Yee
– sequence: 3
  givenname: Hung-Yu
  orcidid: 0000-0002-9035-5408
  surname: Lin
  fullname: Lin, Hung-Yu
– sequence: 4
  givenname: Chia-Wei
  surname: Liou
  fullname: Liou, Chia-Wei
– sequence: 5
  givenname: Pei-Wen
  surname: Wang
  fullname: Wang, Pei-Wen
– sequence: 6
  givenname: Jiin-Haur
  surname: Chuang
  fullname: Chuang, Jiin-Haur
– sequence: 7
  givenname: Shang-Der
  surname: Chen
  fullname: Chen, Shang-Der
– sequence: 8
  givenname: Yao-Chung
  surname: Chuang
  fullname: Chuang, Yao-Chung
– sequence: 9
  givenname: Sheng-Teng
  surname: Huang
  fullname: Huang, Sheng-Teng
– sequence: 10
  givenname: Te-Yao
  surname: Hsu
  fullname: Hsu, Te-Yao
– sequence: 11
  givenname: Cheng-Huei
  surname: Peng
  fullname: Peng, Cheng-Huei
– sequence: 12
  givenname: Min-Yu
  surname: Lan
  fullname: Lan, Min-Yu
BackLink https://www.ncbi.nlm.nih.gov/pubmed/31671122$$D View this record in MEDLINE/PubMed
BookMark eNqNk1uL1DAUx4usuBf9BqIFQXYfZsylVx-EdfEyMLLgqq8hTU-mGdOkNunofHszl12myyLSh5ST3_nnnD_nnEZHxhqIoucYTTHN8ZulHXrD9bQL4SkiJME5fRSd4JKSSUYQPTr4P45OnVsilNIiy55ExxRnOcaEnETrL8pb0VhT94rruF47ORjhlTUuVibWMPy0YAR0Dde2475Zx7-Vb-Kq58o4D23MTR27ToVSYmH7OmStrF5BC8Zv7zQXnnuIQcOKb4Tj8_n7m_nF0-ix5NrBs_15Fn3_-OHb1efJ_PrT7OpyPhFZSfwEU0RoaDhJsaR5VRS0kogDcFIDIYgggFpiVKZ5mdZUcJkmCFdSikTKMquAnkUvd7qdto7tXXMsiKKySApCAzHbEbXlS9b1quX9mlmu2DZg-wXjvVdCAyM5TdOyziTBMhEV5ShJS55mkFJEqSyD1rv9a0PVQi2CCz3XI9HxjVENW9gVywpCclQEgfO9QG9_DeA8a5UToDU3YIdt3ThLyyxJAvrqHvpwd3tqwUMDykgb3hUbUXaZoYQWZZls6p4-QIWvhlaJMGJShfgo4WKUEBgPf_yCD86x2c3X_2evf4zZ1wdsA1z7xlk9bEdyDL44dPrO4tvZDkCyA0RvnetB3iEYsc0K3drFNivE9isU0t7eSxPKbwc3OKL0v5P_AkqjIvk
CitedBy_id crossref_primary_10_3389_fncel_2020_626610
crossref_primary_10_17650_2073_8803_2023_18_2_3_45_51
crossref_primary_10_1080_00325481_2021_1945898
crossref_primary_10_3174_ajnr_A6910
crossref_primary_10_1016_j_ymgmr_2023_101025
crossref_primary_10_1016_j_ymgme_2022_07_002
crossref_primary_10_1007_s00062_021_01030_4
Cites_doi 10.1111/j.1742-4658.2011.08010.x
10.1002/ana.10456
10.1074/jbc.M503062200
10.1074/jbc.M808515200
10.1016/j.cmet.2014.03.011
10.1042/BJ20110795
10.1155/2010/737385
10.1016/j.jns.2016.11.058
10.1055/s-0032-1329395
10.1038/sj.emboj.7601963
10.1016/j.mito.2015.02.006
10.1016/j.bbabio.2016.02.012
10.1016/j.mito.2009.12.141
10.1016/j.ymgme.2004.09.008
10.1016/j.cell.2010.02.026
10.1016/j.mito.2006.05.002
10.1016/j.mito.2016.07.003
10.1016/B978-0-12-386497-0.00001-3
10.1021/bi047527z
10.1038/pr.2016.216
10.1002/glia.22670
10.1111/j.1749-6632.2010.05615.x
10.1083/jcb.143.2.359
10.1093/hmg/ddp281
10.1038/ng2013
10.1016/j.bbrc.2015.04.132
10.1093/hmg/ddx307
10.1016/j.molmed.2017.06.002
10.1016/j.braindev.2012.05.007
10.1111/bpa.12571
10.1155/2017/5691215
ContentType Journal Article
Copyright COPYRIGHT 2019 Public Library of Science
2019 Lin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
2019 Lin et al 2019 Lin et al
Copyright_xml – notice: COPYRIGHT 2019 Public Library of Science
– notice: 2019 Lin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
– notice: 2019 Lin et al 2019 Lin et al
DBID AAYXX
CITATION
CGR
CUY
CVF
ECM
EIF
NPM
IOV
ISR
3V.
7QG
7QL
7QO
7RV
7SN
7SS
7T5
7TG
7TM
7U9
7X2
7X7
7XB
88E
8AO
8C1
8FD
8FE
8FG
8FH
8FI
8FJ
8FK
ABJCF
ABUWG
AEUYN
AFKRA
ARAPS
ATCPS
AZQEC
BBNVY
BENPR
BGLVJ
BHPHI
C1K
CCPQU
D1I
DWQXO
FR3
FYUFA
GHDGH
GNUQQ
H94
HCIFZ
K9.
KB.
KB0
KL.
L6V
LK8
M0K
M0S
M1P
M7N
M7P
M7S
NAPCQ
P5Z
P62
P64
PATMY
PDBOC
PHGZM
PHGZT
PIMPY
PJZUB
PKEHL
PPXIY
PQEST
PQGLB
PQQKQ
PQUKI
PTHSS
PYCSY
RC3
7X8
5PM
DOA
DOI 10.1371/journal.pone.0224173
DatabaseName CrossRef
Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
Gale In Context: Opposing Viewpoints
Gale In Context: Science
ProQuest Central (Corporate)
Animal Behavior Abstracts
Bacteriology Abstracts (Microbiology B)
Biotechnology Research Abstracts
Nursing & Allied Health Database
Ecology Abstracts
Entomology Abstracts (Full archive)
Immunology Abstracts
Meteorological & Geoastrophysical Abstracts
Nucleic Acids Abstracts
Virology and AIDS Abstracts
Agricultural Science Collection
Health & Medical Collection
ProQuest Central (purchase pre-March 2016)
Medical Database (Alumni Edition)
ProQuest Pharma Collection
Public Health Database
Technology Research Database
ProQuest SciTech Collection
ProQuest Technology Collection
ProQuest Natural Science Collection
Hospital Premium Collection
Hospital Premium Collection (Alumni Edition)
ProQuest Central (Alumni) (purchase pre-March 2016)
Materials Science & Engineering Collection
ProQuest Central (Alumni Edition)
ProQuest One Sustainability
ProQuest Central UK/Ireland
Advanced Technologies & Aerospace Collection
Agricultural & Environmental Science Collection
ProQuest Central Essentials
Biological Science Collection
ProQuest Central
Technology Collection
Natural Science Collection
Environmental Sciences and Pollution Management
ProQuest One Community College
ProQuest Materials Science Collection
ProQuest Central Korea
Engineering Research Database
Health Research Premium Collection
Health Research Premium Collection (Alumni)
ProQuest Central Student
AIDS and Cancer Research Abstracts
SciTech Premium Collection
ProQuest Health & Medical Complete (Alumni)
Materials Science Database
Nursing & Allied Health Database (Alumni Edition)
Meteorological & Geoastrophysical Abstracts - Academic
ProQuest Engineering Collection
ProQuest Biological Science Collection
Agricultural Science Database
Health & Medical Collection (Alumni Edition)
Medical Database
Algology Mycology and Protozoology Abstracts (Microbiology C)
Biological Science Database
Engineering Database
Nursing & Allied Health Premium
Advanced Technologies & Aerospace Database
ProQuest Advanced Technologies & Aerospace Collection
Biotechnology and BioEngineering Abstracts
Environmental Science Database
Materials Science Collection
ProQuest Central Premium
ProQuest One Academic (New)
Publicly Available Content Database
ProQuest Health & Medical Research Collection
ProQuest One Academic Middle East (New)
ProQuest One Health & Nursing
ProQuest One Academic Eastern Edition (DO NOT USE)
ProQuest One Applied & Life Sciences
ProQuest One Academic
ProQuest One Academic UKI Edition
Engineering Collection
Environmental Science Collection
Genetics Abstracts
MEDLINE - Academic
PubMed Central (Full Participant titles)
DOAJ Directory of Open Access Journals
DatabaseTitle CrossRef
MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
Agricultural Science Database
Publicly Available Content Database
ProQuest Central Student
ProQuest Advanced Technologies & Aerospace Collection
ProQuest Central Essentials
Nucleic Acids Abstracts
SciTech Premium Collection
Environmental Sciences and Pollution Management
ProQuest One Applied & Life Sciences
ProQuest One Sustainability
Health Research Premium Collection
Meteorological & Geoastrophysical Abstracts
Natural Science Collection
Health & Medical Research Collection
Biological Science Collection
ProQuest Central (New)
ProQuest Medical Library (Alumni)
Engineering Collection
Advanced Technologies & Aerospace Collection
Engineering Database
Virology and AIDS Abstracts
ProQuest Biological Science Collection
ProQuest One Academic Eastern Edition
Agricultural Science Collection
ProQuest Hospital Collection
ProQuest Technology Collection
Health Research Premium Collection (Alumni)
Biological Science Database
Ecology Abstracts
ProQuest Hospital Collection (Alumni)
Biotechnology and BioEngineering Abstracts
Environmental Science Collection
Entomology Abstracts
Nursing & Allied Health Premium
ProQuest Health & Medical Complete
ProQuest One Academic UKI Edition
Environmental Science Database
ProQuest Nursing & Allied Health Source (Alumni)
Engineering Research Database
ProQuest One Academic
Meteorological & Geoastrophysical Abstracts - Academic
ProQuest One Academic (New)
Technology Collection
Technology Research Database
ProQuest One Academic Middle East (New)
Materials Science Collection
ProQuest Health & Medical Complete (Alumni)
ProQuest Central (Alumni Edition)
ProQuest One Community College
ProQuest One Health & Nursing
ProQuest Natural Science Collection
ProQuest Pharma Collection
ProQuest Central
ProQuest Health & Medical Research Collection
Genetics Abstracts
ProQuest Engineering Collection
Biotechnology Research Abstracts
Health and Medicine Complete (Alumni Edition)
ProQuest Central Korea
Bacteriology Abstracts (Microbiology B)
Algology Mycology and Protozoology Abstracts (Microbiology C)
Agricultural & Environmental Science Collection
AIDS and Cancer Research Abstracts
Materials Science Database
ProQuest Materials Science Collection
ProQuest Public Health
ProQuest Nursing & Allied Health Source
ProQuest SciTech Collection
Advanced Technologies & Aerospace Database
ProQuest Medical Library
Animal Behavior Abstracts
Materials Science & Engineering Collection
Immunology Abstracts
ProQuest Central (Alumni)
MEDLINE - Academic
DatabaseTitleList

Agricultural Science Database

MEDLINE

MEDLINE - Academic
Database_xml – sequence: 1
  dbid: DOA
  name: DOAJ Directory of Open Access Journals
  url: https://www.doaj.org/
  sourceTypes: Open Website
– sequence: 2
  dbid: NPM
  name: PubMed
  url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 3
  dbid: EIF
  name: MEDLINE
  url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search
  sourceTypes: Index Database
– sequence: 4
  dbid: 8FG
  name: ProQuest Technology Collection
  url: https://search.proquest.com/technologycollection1
  sourceTypes: Aggregation Database
DeliveryMethod fulltext_linktorsrc
Discipline Sciences (General)
Medicine
DocumentTitleAlternate Mitochondrial dysfunctions in LBSL
EISSN 1932-6203
ExternalDocumentID 2310984823
oai_doaj_org_article_273559d6f21f4cb3a0459a56e53033f9
PMC6822708
A604389949
31671122
10_1371_journal_pone_0224173
Genre Research Support, Non-U.S. Gov't
Journal Article
GeographicLocations United States--US
Taiwan
GeographicLocations_xml – name: Taiwan
– name: United States--US
GrantInformation_xml – fundername: ;
GroupedDBID ---
123
29O
2WC
53G
5VS
7RV
7X2
7X7
7XC
88E
8AO
8C1
8CJ
8FE
8FG
8FH
8FI
8FJ
A8Z
AAFWJ
AAUCC
AAWOE
AAYXX
ABDBF
ABIVO
ABJCF
ABUWG
ACGFO
ACIHN
ACIWK
ACPRK
ACUHS
ADBBV
AEAQA
AENEX
AEUYN
AFKRA
AFPKN
AFRAH
AHMBA
ALIPV
ALMA_UNASSIGNED_HOLDINGS
AOIJS
APEBS
ARAPS
ATCPS
BAWUL
BBNVY
BCNDV
BENPR
BGLVJ
BHPHI
BKEYQ
BPHCQ
BVXVI
BWKFM
CCPQU
CITATION
CS3
D1I
D1J
D1K
DIK
DU5
E3Z
EAP
EAS
EBD
EMOBN
ESX
EX3
F5P
FPL
FYUFA
GROUPED_DOAJ
GX1
HCIFZ
HH5
HMCUK
HYE
IAO
IEA
IGS
IHR
IHW
INH
INR
IOV
IPY
ISE
ISR
ITC
K6-
KB.
KQ8
L6V
LK5
LK8
M0K
M1P
M48
M7P
M7R
M7S
M~E
NAPCQ
O5R
O5S
OK1
OVT
P2P
P62
PATMY
PDBOC
PHGZM
PHGZT
PIMPY
PQQKQ
PROAC
PSQYO
PTHSS
PV9
PYCSY
RNS
RPM
RZL
SV3
TR2
UKHRP
WOQ
WOW
~02
~KM
3V.
ADRAZ
BBORY
CGR
CUY
CVF
ECM
EIF
IPNFZ
NPM
RIG
PMFND
7QG
7QL
7QO
7SN
7SS
7T5
7TG
7TM
7U9
7XB
8FD
8FK
AZQEC
C1K
DWQXO
FR3
GNUQQ
H94
K9.
KL.
M7N
P64
PJZUB
PKEHL
PPXIY
PQEST
PQGLB
PQUKI
RC3
7X8
ESTFP
PUEGO
5PM
AAPBV
ABPTK
BBAFP
ID FETCH-LOGICAL-c692t-13023137451f37b883bf0aeea2de22020eedf1095795d3caf5401bffc4ff96be3
IEDL.DBID DOA
ISSN 1932-6203
IngestDate Sun Oct 02 00:11:10 EDT 2022
Wed Aug 27 01:26:33 EDT 2025
Thu Aug 21 18:23:25 EDT 2025
Fri Sep 05 05:27:33 EDT 2025
Fri Jul 25 11:25:44 EDT 2025
Tue Jun 17 21:20:47 EDT 2025
Tue Jun 10 20:40:59 EDT 2025
Fri Jun 27 04:54:00 EDT 2025
Fri Jun 27 04:17:16 EDT 2025
Thu May 22 21:22:20 EDT 2025
Wed Feb 19 02:31:05 EST 2025
Tue Jul 01 00:52:23 EDT 2025
Thu Apr 24 22:55:56 EDT 2025
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 10
Language English
License This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Creative Commons Attribution License
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c692t-13023137451f37b883bf0aeea2de22020eedf1095795d3caf5401bffc4ff96be3
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
Competing Interests: The authors have declared that no competing interests exist.
ORCID 0000-0002-9035-5408
OpenAccessLink https://doaj.org/article/273559d6f21f4cb3a0459a56e53033f9
PMID 31671122
PQID 2310984823
PQPubID 1436336
PageCount e0224173
ParticipantIDs plos_journals_2310984823
doaj_primary_oai_doaj_org_article_273559d6f21f4cb3a0459a56e53033f9
pubmedcentral_primary_oai_pubmedcentral_nih_gov_6822708
proquest_miscellaneous_2311659644
proquest_journals_2310984823
gale_infotracmisc_A604389949
gale_infotracacademiconefile_A604389949
gale_incontextgauss_ISR_A604389949
gale_incontextgauss_IOV_A604389949
gale_healthsolutions_A604389949
pubmed_primary_31671122
crossref_primary_10_1371_journal_pone_0224173
crossref_citationtrail_10_1371_journal_pone_0224173
ProviderPackageCode CITATION
AAYXX
PublicationCentury 2000
PublicationDate 2019-10-31
PublicationDateYYYYMMDD 2019-10-31
PublicationDate_xml – month: 10
  year: 2019
  text: 2019-10-31
  day: 31
PublicationDecade 2010
PublicationPlace United States
PublicationPlace_xml – name: United States
– name: San Francisco
– name: San Francisco, CA USA
PublicationTitle PloS one
PublicationTitleAlternate PLoS One
PublicationYear 2019
Publisher Public Library of Science
Public Library of Science (PLoS)
Publisher_xml – name: Public Library of Science
– name: Public Library of Science (PLoS)
References GJ Hermann (pone.0224173.ref024) 1998; 143
ME Steenweg (pone.0224173.ref031) 2012; 43
M Picard (pone.0224173.ref001) 2016; 30
M Ruiz (pone.0224173.ref014) 2018; 28
YC Chuang (pone.0224173.ref015) 2017; 2017
RK Dagda (pone.0224173.ref018) 2009; 284
P Mishra (pone.0224173.ref022) 2014; 19
M Aradjanski (pone.0224173.ref029) 2017; 26
GC Scheper (pone.0224173.ref005) 2007; 39
S Wu (pone.0224173.ref023) 2011; 278
Y Miyamoto (pone.0224173.ref012) 2015; 462
L Bonnefond (pone.0224173.ref003) 2005; 44
H Chen (pone.0224173.ref025) 2005; 280
A Malena (pone.0224173.ref027) 2009; 18
SS Yadavalli (pone.0224173.ref019) 2012; 86
L Morató (pone.0224173.ref011) 2014; 62
RJ Rodenburg (pone.0224173.ref013) 2016; 1857
MS van der Knaap (pone.0224173.ref006) 2003; 53
G Twig (pone.0224173.ref021) 2008; 27
R Schoenfeld (pone.0224173.ref030) 2010; 10
P Smits (pone.0224173.ref002) 2010; 2010
HY Lin (pone.0224173.ref017) 2015; 22
L van Berge (pone.0224173.ref028) 2012; 441
H Chen (pone.0224173.ref026) 2010; 141
H Chen (pone.0224173.ref020) 2010; 1201
M Sissler (pone.0224173.ref004) 2017; 23
G Cortopassi (pone.0224173.ref008) 2006; 6
MY Lan (pone.0224173.ref016) 2017; 372
S Yamashita (pone.0224173.ref007) 2013; 35
T Lerman-Sagie (pone.0224173.ref010) 2005; 84
VS Ten (pone.0224173.ref009) 2017; 81
References_xml – volume: 278
  start-page: 941
  year: 2011
  ident: pone.0224173.ref023
  article-title: Mitochondrial oxidative stress causes mitochondrial fragmentation via differential modulation of mitochondrial fission-fusion proteins
  publication-title: FEBS J
  doi: 10.1111/j.1742-4658.2011.08010.x
– volume: 53
  start-page: 252
  year: 2003
  ident: pone.0224173.ref006
  article-title: A new leukoencephalopathy with brainstem and spinal cord involvement and high lactate
  publication-title: Ann Neurol
  doi: 10.1002/ana.10456
– volume: 280
  start-page: 26185
  year: 2005
  ident: pone.0224173.ref025
  article-title: Disruption of fusion results in mitochondrial heterogeneity and dysfunction
  publication-title: J Biol Chem
  doi: 10.1074/jbc.M503062200
– volume: 284
  start-page: 13843
  year: 2009
  ident: pone.0224173.ref018
  article-title: Loss of PINK1 function promotes mitophagy through effects on oxidative stress and mitochondrial fission
  publication-title: J Biol Chem
  doi: 10.1074/jbc.M808515200
– volume: 19
  start-page: 630
  year: 2014
  ident: pone.0224173.ref022
  article-title: Proteolytic cleavage of Opa1 stimulates mitochondrial inner membrane fusion and couples fusion to oxidative phosphorylation
  publication-title: Cell Metab
  doi: 10.1016/j.cmet.2014.03.011
– volume: 441
  start-page: 955
  year: 2012
  ident: pone.0224173.ref028
  article-title: Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation is associated with cell-type-dependent splicing of mtAspRS mRNA
  publication-title: Biochem J
  doi: 10.1042/BJ20110795
– volume: 2010
  start-page: 737385
  year: 2010
  ident: pone.0224173.ref002
  article-title: Mitochondrial translation and beyond: processes implicated in combined oxidative phosphorylation deficiencies
  publication-title: J Biomed Biotechnol
  doi: 10.1155/2010/737385
– volume: 372
  start-page: 229
  year: 2017
  ident: pone.0224173.ref016
  article-title: Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) with a novel DARS2 mutation and isolated progressive spastic paraparesis
  publication-title: J Neurol Sci
  doi: 10.1016/j.jns.2016.11.058
– volume: 43
  start-page: 332
  year: 2012
  ident: pone.0224173.ref031
  article-title: Early-onset LBSL: how severe does it get?
  publication-title: Neuropediatrics
  doi: 10.1055/s-0032-1329395
– volume: 27
  start-page: 433
  year: 2008
  ident: pone.0224173.ref021
  article-title: Fission and selective fusion govern mitochondrial segregation and elimination by autophagy
  publication-title: EMBO J
  doi: 10.1038/sj.emboj.7601963
– volume: 22
  start-page: 31
  year: 2015
  ident: pone.0224173.ref017
  article-title: Mitochondrial transfer from Wharton’s jelly-derived mesenchymal stem cells to mitochondria-defective cells recaptures impaired mitochondrial function
  publication-title: Mitochondrion
  doi: 10.1016/j.mito.2015.02.006
– volume: 1857
  start-page: 938
  year: 2016
  ident: pone.0224173.ref013
  article-title: Mitochondrial complex I-linked disease
  publication-title: Biochim Biophys Acta
  doi: 10.1016/j.bbabio.2016.02.012
– volume: 10
  start-page: 143
  year: 2010
  ident: pone.0224173.ref030
  article-title: Oligodendroglial differentiation induces mitochondrial genes and inhibition of mitochondrial function represses oligodendroglial differentiation
  publication-title: Mitochondrion
  doi: 10.1016/j.mito.2009.12.141
– volume: 84
  start-page: 127
  year: 2005
  ident: pone.0224173.ref010
  article-title: White matter involvement in mitochondrial diseases
  publication-title: Mol Genet Metab
  doi: 10.1016/j.ymgme.2004.09.008
– volume: 141
  start-page: 280
  year: 2010
  ident: pone.0224173.ref026
  article-title: Mitochondrial fusion is required for mtDNA stability in skeletal muscle and tolerance of mtDNA mutations
  publication-title: Cell
  doi: 10.1016/j.cell.2010.02.026
– volume: 6
  start-page: 161
  year: 2006
  ident: pone.0224173.ref008
  article-title: Mitochondrial disease activates transcripts of the unfolded protein response and cell cycle and inhibits vesicular secretion and oligodendrocyte-specific transcripts
  publication-title: Mitochondrion
  doi: 10.1016/j.mito.2006.05.002
– volume: 30
  start-page: 105
  year: 2016
  ident: pone.0224173.ref001
  article-title: The rise of mitochondria in medicine
  publication-title: Mitochondrion
  doi: 10.1016/j.mito.2016.07.003
– volume: 86
  start-page: 1
  year: 2012
  ident: pone.0224173.ref019
  article-title: Quality control in aminoacyl-tRNA synthesis its role in translational fidelity
  publication-title: Adv Protein Chem Struct Biol
  doi: 10.1016/B978-0-12-386497-0.00001-3
– volume: 44
  start-page: 4805
  year: 2005
  ident: pone.0224173.ref003
  article-title: Toward the full set of human mitochondrial aminoacyl-tRNA synthetases: characterization of AspRS and TyrRS
  publication-title: Biochemistry
  doi: 10.1021/bi047527z
– volume: 81
  start-page: 286
  year: 2017
  ident: pone.0224173.ref009
  article-title: Mitochondrial dysfunction in alveolar and white matter developmental failure in premature infants
  publication-title: Pediatr Res
  doi: 10.1038/pr.2016.216
– volume: 62
  start-page: 1878
  year: 2014
  ident: pone.0224173.ref011
  article-title: Mitochondrial dysfunction in central nervous system white matter disorders
  publication-title: Glia
  doi: 10.1002/glia.22670
– volume: 1201
  start-page: 21
  year: 2010
  ident: pone.0224173.ref020
  article-title: Physiological functions of mitochondrial fusion
  publication-title: Ann N Y Acad Sci
  doi: 10.1111/j.1749-6632.2010.05615.x
– volume: 143
  start-page: 359
  year: 1998
  ident: pone.0224173.ref024
  article-title: Mitochondrial fusion in yeast requires the transmembrane GTPase Fzo1p
  publication-title: J Cell Biol
  doi: 10.1083/jcb.143.2.359
– volume: 18
  start-page: 3407
  year: 2009
  ident: pone.0224173.ref027
  article-title: Inhibition of mitochondrial fission favours mutant over wild-type mitochondrial DNA
  publication-title: Hum Mol Genet
  doi: 10.1093/hmg/ddp281
– volume: 39
  start-page: 534
  year: 2007
  ident: pone.0224173.ref005
  article-title: Mitochondrial aspartyl-tRNA synthetase deficiency causes leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation
  publication-title: Nat Genet
  doi: 10.1038/ng2013
– volume: 462
  start-page: 275
  year: 2015
  ident: pone.0224173.ref012
  article-title: Hypomyelinating leukodystrophy-associated missense mutation in HSPD1 blunts mitochondrial dynamics
  publication-title: Biochem Biophys Res Commun
  doi: 10.1016/j.bbrc.2015.04.132
– volume: 26
  start-page: 4181
  year: 2017
  ident: pone.0224173.ref029
  article-title: DARS2 protects against neuroinflammation and apoptotic neuronal loss, but is dispensable for myelin producing cells
  publication-title: Hum Mol Genet
  doi: 10.1093/hmg/ddx307
– volume: 23
  start-page: 693
  year: 2017
  ident: pone.0224173.ref004
  article-title: Recent Advances in Mitochondrial Aminoacyl-tRNA Synthetases and Disease
  publication-title: Trends Mol Med
  doi: 10.1016/j.molmed.2017.06.002
– volume: 35
  start-page: 312
  year: 2013
  ident: pone.0224173.ref007
  article-title: Neuropathology of leukoencephalopathy with brainstem and spinal cord involvement and high lactate caused by a homozygous mutation of DARS2
  publication-title: Brain Dev
  doi: 10.1016/j.braindev.2012.05.007
– volume: 28
  start-page: 611
  year: 2018
  ident: pone.0224173.ref014
  article-title: Oxidative stress and mitochondrial dynamics malfunction are linked in Pelizaeus-Merzbacher disease
  publication-title: Brain Pathol
  doi: 10.1111/bpa.12571
– volume: 2017
  start-page: 5691215
  year: 2017
  ident: pone.0224173.ref015
  article-title: Mitochondrial Transfer from Wharton’s Jelly Mesenchymal Stem Cell to MERRF Cybrid Reduces Oxidative Stress and Improves Mitochondrial Bioenergetics
  publication-title: Oxid Med Cell Longev
  doi: 10.1155/2017/5691215
SSID ssj0053866
Score 2.3631194
Snippet Several inherited human diseases have been linked to mitochondrial aminoacyl-tRNA synthetases (mtARSs). Leukoencephalopathy with brainstem and spinal cord...
SourceID plos
doaj
pubmedcentral
proquest
gale
pubmed
crossref
SourceType Open Website
Open Access Repository
Aggregation Database
Index Database
Enrichment Source
StartPage e0224173
SubjectTerms Aminoacyl-tRNA synthetases
Aspartate-tRNA ligase
Aspartate-tRNA Ligase - deficiency
Aspartate-tRNA Ligase - genetics
Base Sequence
Bioenergetics
Biology and Life Sciences
Biosynthesis
Brain stem
Chains
Deoxyribonucleic acid
Disease
DNA
EDTA
Electron transport
Elongation
Fibroblasts
Fibroblasts - pathology
Gene mutation
Genes
Genetic aspects
Hospitals
Humans
Lactates
Lactic acid
Leukodystrophy
Leukoencephalopathies - genetics
Leukoencephalopathies - pathology
Leukoencephalopathy
Ligases
Maintenance
Medical schools
Medicine
Medicine and Health Sciences
Mitochondria
Mitochondria - pathology
Mitochondrial diseases
Mitochondrial Diseases - genetics
Mitochondrial Diseases - pathology
Mitochondrial DNA
Morphology
Mutation
Neurology
Oxidative stress
Oxygen
Oxygen consumption
Pediatrics
Physiology
Proteins
RNA
Spinal cord
Transfer RNA
Translations
tRNA
SummonAdditionalLinks – databaseName: ProQuest Technology Collection
  dbid: 8FG
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV1bb9MwFLagSIgXtI3LygYYhMT2kK2JHSd-QhuiDLSBxBjaW-T4sk1USVjah_57znHcQNAEvNbHVXuun2_fIeRVgnsbcqKjOJuUEc-FjUCSR0Y7JhUvmTH-tsUncXTGP56n52HDrQ3XKlc50SdqU2vcI99HHCJznifsTfMjwq5ReLoaWmjcJnfiBDwJX4pP368yMcSyEOG5HMvi_WCdvaau7J6vXRkblCPP2t_n5lEzq9ubgOef9yd_K0jTNXI_IEl60Jl-ndyy1Qa5exLOyjfIegjblu4EbundB2R5AhEMGa8y6HjULFssbN736FVFZ3bxvcZJzaWa1diteElxp5aW2EkCOZ-pqgxtG-ylRXHhCrMgwXnS8bkfmymN-JXiu3VvdbpzfHh6vPuQnE3ffX17FIXuC5EWMsEe9UgNxzKexo5lZZ6z0k2UtSoxNkkAZUJ1dWCTNJOpYVo5wH5x6ZzmzklRWvaIjCrQ9CahivHcZIBlSsV5yp1yTlntUi0SiHqTjAlbGaHQgZocO2TMCn_elsESpdNpgaYrgunGJOpnNR01xz_kD9G-vSwSa_sP6uuLIsRpAWgO1lhGuCR2XJdMAeSVKhU2hVrPnByT5-gdRfdKtU8PxYHAI1UpOUi89BJIrlHh7Z0LtWjb4sPnb_8hdPplIPQ6CLka1KFVeDEB_wlJuwaS2wNJSBF6MLyJvrzSSlv8CiaYufLvm4df9MP4pXgjr7L1wsvEIpUAp8fkcRcOvWaRXQFwPNg1GwTKQPXDkerq0nObCwCs2SR_8veftUXuAXCVHYbYJqP59cI-BXA4L5_5DPATVO9mzw
  priority: 102
  providerName: ProQuest
– databaseName: Scholars Portal Journals: Open Access
  dbid: M48
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV3Nb9MwFLdGuXBBjK8VChiExHZIlcSOEx8Q2hDTQBtIjKLdIscf20SUlKaV6H_Pe04aEVQEB06V4vcq5X34_Rzbv0fIyxi_bchQB1EaFgHPhA1AkgdGOyYVL5gx_rTFR3Ey4x8ukosdsunZ2hmw2bq0w35Ss0U5_fF9_QYS_rXv2pBGG6XpvK7s1NeklN0gN-E3xjg_4_2-AmS3EN0Fuj9pDgqU5_HvZ-vRvKybbVD09xOVv5So4zvkdoct6WEbDLtkx1Z3yW6XvQ3d7yimD-6R9RkkMrx7ZTD-qFk3WN98CNLripZ29a1GpfmVKmtsWrym-MGWFthQAqmfqaoMbebYUovi-hW0YJ7z3ONLP1YqjTCW4vV173y6f3p0fnpwn8yO3315exJ0TRgCLWSMreqRIY6lPIkcS4ssY4ULlbUqNjaOAWxCkXVRiLt9iWFaOYCAUeGc5s5JUVj2gIwqMO8eoYrxzKQAaQrFecKdck5Z7RItYkh-E48J21g-1x1DOTbKKHO_7ZbCSqU1ZI7-yjt_jUnQa81bho6_yB-hU3tZ5Nf2D-rFZd6law6gDpZaRrg4clwXTAHylSoRNoGSz5wck2cYEnl7WbWfJfJDgTurUnKQeOElkGOjwkM8l2rVNPn7T1__Qej880DoVSfkajCHVt3FCXgn5O4aSE4GkjBT6MHwHgbwxipNjtheZjyLwSiTTVBvH37eD-Of4sG8ytYrLxOJRAKqHpOHbQ70lkWSBYDz4Nd0kB0D0w9HqusrT3EuALemYfbof_jqMbkFKFe2gGNCRsvFyj4BJLksnvrJ4ScegXXu
  priority: 102
  providerName: Scholars Portal
Title Mitochondrial dysfunctions in leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL)
URI https://www.ncbi.nlm.nih.gov/pubmed/31671122
https://www.proquest.com/docview/2310984823
https://www.proquest.com/docview/2311659644
https://pubmed.ncbi.nlm.nih.gov/PMC6822708
https://doaj.org/article/273559d6f21f4cb3a0459a56e53033f9
http://dx.doi.org/10.1371/journal.pone.0224173
Volume 14
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
journalDatabaseRights – providerCode: PRVFSB
  databaseName: Free Full-Text Journals in Chemistry
  customDbUrl:
  eissn: 1932-6203
  dateEnd: 99991231
  omitProxy: true
  ssIdentifier: ssj0053866
  issn: 1932-6203
  databaseCode: HH5
  dateStart: 20060101
  isFulltext: true
  titleUrlDefault: http://abc-chemistry.org/
  providerName: ABC ChemistRy
– providerCode: PRVAFT
  databaseName: Open Access Digital Library
  customDbUrl:
  eissn: 1932-6203
  dateEnd: 99991231
  omitProxy: true
  ssIdentifier: ssj0053866
  issn: 1932-6203
  databaseCode: KQ8
  dateStart: 20060101
  isFulltext: true
  titleUrlDefault: http://grweb.coalliance.org/oadl/oadl.html
  providerName: Colorado Alliance of Research Libraries
– providerCode: PRVAFT
  databaseName: Open Access Digital Library
  customDbUrl:
  eissn: 1932-6203
  dateEnd: 99991231
  omitProxy: true
  ssIdentifier: ssj0053866
  issn: 1932-6203
  databaseCode: KQ8
  dateStart: 20061001
  isFulltext: true
  titleUrlDefault: http://grweb.coalliance.org/oadl/oadl.html
  providerName: Colorado Alliance of Research Libraries
– providerCode: PRVAON
  databaseName: DOAJ Directory of Open Access Journals
  customDbUrl:
  eissn: 1932-6203
  dateEnd: 99991231
  omitProxy: true
  ssIdentifier: ssj0053866
  issn: 1932-6203
  databaseCode: DOA
  dateStart: 20060101
  isFulltext: true
  titleUrlDefault: https://www.doaj.org/
  providerName: Directory of Open Access Journals
– providerCode: PRVEBS
  databaseName: Academic Search Ultimate - eBooks
  customDbUrl: https://search.ebscohost.com/login.aspx?authtype=ip,shib&custid=s3936755&profile=ehost&defaultdb=asn
  eissn: 1932-6203
  dateEnd: 99991231
  omitProxy: true
  ssIdentifier: ssj0053866
  issn: 1932-6203
  databaseCode: ABDBF
  dateStart: 20080101
  isFulltext: true
  titleUrlDefault: https://search.ebscohost.com/direct.asp?db=asn
  providerName: EBSCOhost
– providerCode: PRVBFR
  databaseName: Free Medical Journals
  customDbUrl:
  eissn: 1932-6203
  dateEnd: 99991231
  omitProxy: true
  ssIdentifier: ssj0053866
  issn: 1932-6203
  databaseCode: DIK
  dateStart: 20060101
  isFulltext: true
  titleUrlDefault: http://www.freemedicaljournals.com
  providerName: Flying Publisher
– providerCode: PRVFQY
  databaseName: GFMER Free Medical Journals
  customDbUrl:
  eissn: 1932-6203
  dateEnd: 99991231
  omitProxy: true
  ssIdentifier: ssj0053866
  issn: 1932-6203
  databaseCode: GX1
  dateStart: 20060101
  isFulltext: true
  titleUrlDefault: http://www.gfmer.ch/Medical_journals/Free_medical.php
  providerName: Geneva Foundation for Medical Education and Research
– providerCode: PRVHPJ
  databaseName: ROAD: Directory of Open Access Scholarly Resources
  customDbUrl:
  eissn: 1932-6203
  dateEnd: 99991231
  omitProxy: true
  ssIdentifier: ssj0053866
  issn: 1932-6203
  databaseCode: M~E
  dateStart: 20060101
  isFulltext: true
  titleUrlDefault: https://road.issn.org
  providerName: ISSN International Centre
– providerCode: PRVAQN
  databaseName: PubMed Central
  customDbUrl:
  eissn: 1932-6203
  dateEnd: 99991231
  omitProxy: true
  ssIdentifier: ssj0053866
  issn: 1932-6203
  databaseCode: RPM
  dateStart: 20060101
  isFulltext: true
  titleUrlDefault: https://www.ncbi.nlm.nih.gov/pmc/
  providerName: National Library of Medicine
– providerCode: PRVPQU
  databaseName: Health & Medical Collection
  customDbUrl:
  eissn: 1932-6203
  dateEnd: 99991231
  omitProxy: true
  ssIdentifier: ssj0053866
  issn: 1932-6203
  databaseCode: 7X7
  dateStart: 20061201
  isFulltext: true
  titleUrlDefault: https://search.proquest.com/healthcomplete
  providerName: ProQuest
– providerCode: PRVPQU
  databaseName: ProQuest Central
  customDbUrl: http://www.proquest.com/pqcentral?accountid=15518
  eissn: 1932-6203
  dateEnd: 99991231
  omitProxy: true
  ssIdentifier: ssj0053866
  issn: 1932-6203
  databaseCode: BENPR
  dateStart: 20061201
  isFulltext: true
  titleUrlDefault: https://www.proquest.com/central
  providerName: ProQuest
– providerCode: PRVPQU
  databaseName: ProQuest Technology Collection
  customDbUrl:
  eissn: 1932-6203
  dateEnd: 99991231
  omitProxy: true
  ssIdentifier: ssj0053866
  issn: 1932-6203
  databaseCode: 8FG
  dateStart: 20061201
  isFulltext: true
  titleUrlDefault: https://search.proquest.com/technologycollection1
  providerName: ProQuest
– providerCode: PRVPQU
  databaseName: Public Health Database
  customDbUrl:
  eissn: 1932-6203
  dateEnd: 99991231
  omitProxy: true
  ssIdentifier: ssj0053866
  issn: 1932-6203
  databaseCode: 8C1
  dateStart: 20061201
  isFulltext: true
  titleUrlDefault: https://search.proquest.com/publichealth
  providerName: ProQuest
– providerCode: PRVFZP
  databaseName: Scholars Portal Journals: Open Access
  customDbUrl:
  eissn: 1932-6203
  dateEnd: 20250930
  omitProxy: true
  ssIdentifier: ssj0053866
  issn: 1932-6203
  databaseCode: M48
  dateStart: 20061201
  isFulltext: true
  titleUrlDefault: http://journals.scholarsportal.info
  providerName: Scholars Portal
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV3Nb9MwFLegXLggxtcKpRiExHbIlsSOkxzXaWWgbaCNod4ixx_bRJVUpD30v-c9x40WNGkcuORQP1ft-_w5tn-PkI8xvtvIQxVEaVgGPBMmAEkeaGVZLnnJtHanLc7E8SX_Oktmt1p94Zmwlh64Vdw-lFcAvVrYOLJclUwCBsllIkwCyZdZd3UPythmMdXmYIhiIfxFOZZG-94ue4u6MnuuaqWsV4gcX3-XlQeLed3cBTn_Pjl5qxRNn5InHkPSg_a3b5EHpnpGtnyUNnTHU0nvPifrUwhYSHCVRj-jet1gHXOuRm8qOjerXzVOWlzLeY3NidcUX8zSEhtHIMUzlZWmzQJbZ1Fcp8IsyGeOY3zpxuZSIVyleE3dGZnunEwuTnZfkMvp0Y_D48A3WwiUyGNsSY9McCzlSWRZWmYZK20ojZGxNnEMoBKKqY1C3NVLNFPSAtSLSmsVtzYXpWEvyaAC9W4TKhnPdArQpZScJ9xKa6VRNlEihiDX8ZCwjeYL5ZnIsSHGvHDbaymsSFpFFmivwttrSIJu1qJl4rhHfoJG7WSRR9t9AN5VeO8q7vOuIXmHLlG0l1K7bFAcCNxBzXMOEh-cBHJpVHhY50qumqb48u3nPwhdnPeEPnkhW4M6lPQXJOA_IUdXT3LUk4SMoHrD2-jAG600BWL4PONZDEoZbZz67uH33TB-KR7Aq0y9cjKRSHJAz0Pyqo2BTrNIpgCwHeya9qKjp_r-SHVz7ajMBeDTNMxe_w9bvSGPAc3mLbAYkcHy98q8BcS4LMfkYTpL4ZkdRvicfh6TR5Ojs-_nY5c24HnKsz9W5nAp
linkProvider Directory of Open Access Journals
linkToHtml http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV1Lb9NAEF6VIAEXRMujgUIXBKI9uI2968ceEGqBqqFJkehDuZn1eretiGxTJ0L5U_xGZtYPMKqAS6_ZWSeZGX_zzT5mCHnp4dqGGCjHDQeJw6NAOyDJnVQZJiRPWJra0xaHwf4J_zjxJ0vkR3MXBo9VNphogTrNFa6RbyMPERGPPPa2-OZg1yjcXW1aaFRucaAX3yFlK98M34N9X3ne3ofjd_tO3VXAUYHwsPc6ljxjIfddw8IkilhiBlJr6aXa84A9QdQw8F1-KPyUKWmA07iJMYobI4JEM3juDXKTswHHWv3hpE3wADuCoL6ex0J3u_aGrSLP9JaNlSHrhD_bJaCNBb1impdXEd0_z2v-FgD37pG7NXOlO5WrLZMlna2QW-N6b36FLNcwUdKNupb15n2yGANiAMJmKTo6TRclBlLr6_Qio1M9_5rjpOJcTnPsjryguDJME-xcgTWmqcxSWhbYu4tiogyzAFBtkfOZHZtKhXyZ4j1562V0Y7R7NNp8QE6uxS4PSS8DTa8SKhmP0hC4UyI597mRxkitjK8CD1Am9fqENUaIVV0KHTtyTGO7vxdCSlTpNEbTxbXp-sRpZxVVKZB_yO-ifVtZLORtP8gvz-IaF2Jgj5DTpYHxXMNVwiRQbCH9QPvALZgRfbKO3hFXt2JbOIp3AtzCFYKDxAsrgcU8MjwtdCbnZRkPP53-h9DR547Q61rI5KAOJesbGvCfsEhYR3KtIwmQpDrDq-jLjVbK-NfLCzMb_756-Hk7jA_FE4CZzudWxg18AfS9Tx5Vr0OrWazmAHkD2DXsvCgd1XdHsotzW0s9AIIcDqLHf_9Z6-T2_vF4FI-GhwdPyB0gzaLiL2ukN7uc66dATGfJM4sGlHy5bvj5CeQrpBk
linkToPdf http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV3db9MwELdGkSZeEBsfKwxmEIjtIWsTO18PCG2MamPdQIyhvgXHsbeJKglLK9R_jb-OO8cJBE3Ay17rc9renX_-XXy-I-S5h-824qF03HCYOjwKlAOS3MmkZrHgKcsyk21xHOyf8ncTf7JEfjR3YTCtssFEA9RZIfEd-QB5SBzxyGMDbdMiPuyNXpffHOwghSetTTuN2kUO1eI7hG_Vq4M9sPULzxu9_fRm37EdBhwZxB72YcfyZyzkvqtZmEYRS_VQKCW8THkeMCnYQTR8rx_Gfsak0MBv3FRrybWOg1QxeO4NcjNknGE6WThpgz3AkSCwV_VY6A6sZ2yXRa62zb4Zss5WaDoGtPtCr5wW1VWk98_czd82w9EdctuyWLpTu90KWVL5Klk-suf0q2TFQkZFN21d6627ZHEE6AFom2fo9DRbVLipGr-nFzmdqvnXAieV52JaYKfkBcW3xDTFLhZYb5qKPKNViX28KAbNMAvA1RQ8n5mxqZDInSnemTceRzfHuyfjrXvk9Frscp_0ctD0GqGC8SgLgUelgnOfa6G1UFL7MvAAcTKvT1hjhETasujYnWOamLO-EMKjWqcJmi6xpusTp51V1mVB_iG_i_ZtZbGot_mguDxLLEYkwCQhvssC7bmay5QJoNux8APlA89gOu6TDfSOpL4h20JTshPgcW4cc5B4ZiSwsEeOS-RMzKsqOXj_-T-ETj52hF5aIV2AOqSwtzXgP2HBsI7kekcS4El2htfQlxutVMmvhQwzG_--evhpO4wPxWzAXBVzI-MGfgxUvk8e1Muh1SxWdoAYAuwadhZKR_Xdkfzi3NRVD4Ash8Po4d9_1gZZBuBJxgfHh4_ILeDPcU1l1klvdjlXj4GjztInBgwo-XLd6PMTlEmoVA
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Mitochondrial+dysfunctions+in+leukoencephalopathy+with+brainstem+and+spinal+cord+involvement+and+lactate+elevation+%28LBSL%29&rft.jtitle=PloS+one&rft.au=Tsu-Kung+Lin&rft.au=Yung-Yee+Chang&rft.au=Hung-Yu+Lin&rft.au=Chia-Wei+Liou&rft.date=2019-10-31&rft.pub=Public+Library+of+Science+%28PLoS%29&rft.eissn=1932-6203&rft.volume=14&rft.issue=10&rft.spage=e0224173&rft_id=info:doi/10.1371%2Fjournal.pone.0224173&rft.externalDBID=DOA&rft.externalDocID=oai_doaj_org_article_273559d6f21f4cb3a0459a56e53033f9
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1932-6203&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1932-6203&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1932-6203&client=summon