Mitochondrial DNA mutations in human colonic crypt stem cells

The mitochondrial genome encodes 13 essential subunits of the respiratory chain and has remarkable genetics based on uniparental inheritance. Within human populations, the mitochondrial genome has a high rate of sequence divergence with multiple polymorphic variants and thus has played a major role...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:The Journal of clinical investigation 2003-11, Vol.112 (9), p.1351-1360
Hauptverfasser: Taylor, Robert W, Barron, Martin J, Borthwick, Gillian M, Gospel, Amy, Chinnery, Patrick F, Samuels, David C, Taylor, Geoffrey A, Plusa, Stefan M, Needham, Stephanie J, Greaves, Laura C, Kirkwood, Thomas B L, Turnbull, Douglass M
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 1360
container_issue 9
container_start_page 1351
container_title The Journal of clinical investigation
container_volume 112
creator Taylor, Robert W
Barron, Martin J
Borthwick, Gillian M
Gospel, Amy
Chinnery, Patrick F
Samuels, David C
Taylor, Geoffrey A
Plusa, Stefan M
Needham, Stephanie J
Greaves, Laura C
Kirkwood, Thomas B L
Turnbull, Douglass M
description The mitochondrial genome encodes 13 essential subunits of the respiratory chain and has remarkable genetics based on uniparental inheritance. Within human populations, the mitochondrial genome has a high rate of sequence divergence with multiple polymorphic variants and thus has played a major role in examining the evolutionary history of our species. In recent years it has also become apparent that pathogenic mitochondrial DNA (mtDNA) mutations play an important role in neurological and other diseases. Patients harbor many different mtDNA mutations, some of which are mtDNA mutations, some of which are inherited, but others that seem to be sporadic. It has also been suggested that mtDNA mutations play a role in aging and cancer, but the evidence for a causative role in these conditions is less clear. The accumulated data would suggest, however, that mtDNA mutations occur on a frequent basis. In this article we describe a new phenomenon: the accumulation of mtDNA mutations in human colonic crypt stem cells that result in a significant biochemical defect in their progeny. These studies have important consequences not only for understanding of the finding of mtDNA mutations in aging tissues and tumors, but also for determining the frequency of mtDNA mutations within a cell.
doi_str_mv 10.1172/jci19435
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_71339962</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>475759691</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3605-1ffcd1ae416f198c73be9a021091bb01f459bb76e4141d3e301d0539d61bb7043</originalsourceid><addsrcrecordid>eNpdkDtPwzAURi0EoqUg8QuQxYBYAr6xHccDQ1VeRQUWmCPHcVRXSVzsZOi_x31ISEx3uEdHRx9Cl0DuAER6v9IWJKP8CI2B8zzJU5ofozEhKSRS0HyEzkJYEQKMcXaKRsC4FCKDMXp4t73TS9dV3qoGP35McTv0qreuC9h2eDm0qsPaNa6zGmu_Wfc49KbF2jRNOEcntWqCuTjcCfp-fvqavSaLz5f5bLpINM0IT6CudQXKMMhqkLkWtDRSxTgioSwJ1DGnLEUWAQYVNZRARTiVVRbfgjA6QTd779q7n8GEvmht2BaozrghFAIolTJLI3j9D1y5wXexrUgJ4ZDBzna7h7R3IXhTF2tvW-U3BZBiu2fxNpvv9ozo1cE3lK2p_sDDgPQXX5ltzQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>200516104</pqid></control><display><type>article</type><title>Mitochondrial DNA mutations in human colonic crypt stem cells</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Taylor, Robert W ; Barron, Martin J ; Borthwick, Gillian M ; Gospel, Amy ; Chinnery, Patrick F ; Samuels, David C ; Taylor, Geoffrey A ; Plusa, Stefan M ; Needham, Stephanie J ; Greaves, Laura C ; Kirkwood, Thomas B L ; Turnbull, Douglass M</creator><creatorcontrib>Taylor, Robert W ; Barron, Martin J ; Borthwick, Gillian M ; Gospel, Amy ; Chinnery, Patrick F ; Samuels, David C ; Taylor, Geoffrey A ; Plusa, Stefan M ; Needham, Stephanie J ; Greaves, Laura C ; Kirkwood, Thomas B L ; Turnbull, Douglass M</creatorcontrib><description>The mitochondrial genome encodes 13 essential subunits of the respiratory chain and has remarkable genetics based on uniparental inheritance. Within human populations, the mitochondrial genome has a high rate of sequence divergence with multiple polymorphic variants and thus has played a major role in examining the evolutionary history of our species. In recent years it has also become apparent that pathogenic mitochondrial DNA (mtDNA) mutations play an important role in neurological and other diseases. Patients harbor many different mtDNA mutations, some of which are mtDNA mutations, some of which are inherited, but others that seem to be sporadic. It has also been suggested that mtDNA mutations play a role in aging and cancer, but the evidence for a causative role in these conditions is less clear. The accumulated data would suggest, however, that mtDNA mutations occur on a frequent basis. In this article we describe a new phenomenon: the accumulation of mtDNA mutations in human colonic crypt stem cells that result in a significant biochemical defect in their progeny. These studies have important consequences not only for understanding of the finding of mtDNA mutations in aging tissues and tumors, but also for determining the frequency of mtDNA mutations within a cell.</description><identifier>ISSN: 0021-9738</identifier><identifier>EISSN: 1558-8238</identifier><identifier>DOI: 10.1172/jci19435</identifier><identifier>PMID: 14597761</identifier><language>eng</language><publisher>United States: American Society for Clinical Investigation</publisher><subject>Aged ; Aged, 80 and over ; Aging ; Bats ; Biomedical research ; Cancer ; Colon - cytology ; Colon - metabolism ; Cytochrome ; Dehydrogenases ; Disease ; DNA Replication ; DNA, Mitochondrial - genetics ; Electron Transport ; Genomes ; Humans ; Mathematics ; Middle Aged ; Mitochondria ; Mitochondrial DNA ; Models, Genetic ; Mutation ; Phosphorylation ; Proteins ; Stem cells ; Stem Cells - metabolism ; Transfer RNA ; Tumors</subject><ispartof>The Journal of clinical investigation, 2003-11, Vol.112 (9), p.1351-1360</ispartof><rights>Copyright American Society for Clinical Investigation Nov 2003</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3605-1ffcd1ae416f198c73be9a021091bb01f459bb76e4141d3e301d0539d61bb7043</citedby><cites>FETCH-LOGICAL-c3605-1ffcd1ae416f198c73be9a021091bb01f459bb76e4141d3e301d0539d61bb7043</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,782,786,27931,27932</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14597761$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Taylor, Robert W</creatorcontrib><creatorcontrib>Barron, Martin J</creatorcontrib><creatorcontrib>Borthwick, Gillian M</creatorcontrib><creatorcontrib>Gospel, Amy</creatorcontrib><creatorcontrib>Chinnery, Patrick F</creatorcontrib><creatorcontrib>Samuels, David C</creatorcontrib><creatorcontrib>Taylor, Geoffrey A</creatorcontrib><creatorcontrib>Plusa, Stefan M</creatorcontrib><creatorcontrib>Needham, Stephanie J</creatorcontrib><creatorcontrib>Greaves, Laura C</creatorcontrib><creatorcontrib>Kirkwood, Thomas B L</creatorcontrib><creatorcontrib>Turnbull, Douglass M</creatorcontrib><title>Mitochondrial DNA mutations in human colonic crypt stem cells</title><title>The Journal of clinical investigation</title><addtitle>J Clin Invest</addtitle><description>The mitochondrial genome encodes 13 essential subunits of the respiratory chain and has remarkable genetics based on uniparental inheritance. Within human populations, the mitochondrial genome has a high rate of sequence divergence with multiple polymorphic variants and thus has played a major role in examining the evolutionary history of our species. In recent years it has also become apparent that pathogenic mitochondrial DNA (mtDNA) mutations play an important role in neurological and other diseases. Patients harbor many different mtDNA mutations, some of which are mtDNA mutations, some of which are inherited, but others that seem to be sporadic. It has also been suggested that mtDNA mutations play a role in aging and cancer, but the evidence for a causative role in these conditions is less clear. The accumulated data would suggest, however, that mtDNA mutations occur on a frequent basis. In this article we describe a new phenomenon: the accumulation of mtDNA mutations in human colonic crypt stem cells that result in a significant biochemical defect in their progeny. These studies have important consequences not only for understanding of the finding of mtDNA mutations in aging tissues and tumors, but also for determining the frequency of mtDNA mutations within a cell.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Aging</subject><subject>Bats</subject><subject>Biomedical research</subject><subject>Cancer</subject><subject>Colon - cytology</subject><subject>Colon - metabolism</subject><subject>Cytochrome</subject><subject>Dehydrogenases</subject><subject>Disease</subject><subject>DNA Replication</subject><subject>DNA, Mitochondrial - genetics</subject><subject>Electron Transport</subject><subject>Genomes</subject><subject>Humans</subject><subject>Mathematics</subject><subject>Middle Aged</subject><subject>Mitochondria</subject><subject>Mitochondrial DNA</subject><subject>Models, Genetic</subject><subject>Mutation</subject><subject>Phosphorylation</subject><subject>Proteins</subject><subject>Stem cells</subject><subject>Stem Cells - metabolism</subject><subject>Transfer RNA</subject><subject>Tumors</subject><issn>0021-9738</issn><issn>1558-8238</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNpdkDtPwzAURi0EoqUg8QuQxYBYAr6xHccDQ1VeRQUWmCPHcVRXSVzsZOi_x31ISEx3uEdHRx9Cl0DuAER6v9IWJKP8CI2B8zzJU5ofozEhKSRS0HyEzkJYEQKMcXaKRsC4FCKDMXp4t73TS9dV3qoGP35McTv0qreuC9h2eDm0qsPaNa6zGmu_Wfc49KbF2jRNOEcntWqCuTjcCfp-fvqavSaLz5f5bLpINM0IT6CudQXKMMhqkLkWtDRSxTgioSwJ1DGnLEUWAQYVNZRARTiVVRbfgjA6QTd779q7n8GEvmht2BaozrghFAIolTJLI3j9D1y5wXexrUgJ4ZDBzna7h7R3IXhTF2tvW-U3BZBiu2fxNpvv9ozo1cE3lK2p_sDDgPQXX5ltzQ</recordid><startdate>200311</startdate><enddate>200311</enddate><creator>Taylor, Robert W</creator><creator>Barron, Martin J</creator><creator>Borthwick, Gillian M</creator><creator>Gospel, Amy</creator><creator>Chinnery, Patrick F</creator><creator>Samuels, David C</creator><creator>Taylor, Geoffrey A</creator><creator>Plusa, Stefan M</creator><creator>Needham, Stephanie J</creator><creator>Greaves, Laura C</creator><creator>Kirkwood, Thomas B L</creator><creator>Turnbull, Douglass M</creator><general>American Society for Clinical Investigation</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>S0X</scope><scope>7X8</scope></search><sort><creationdate>200311</creationdate><title>Mitochondrial DNA mutations in human colonic crypt stem cells</title><author>Taylor, Robert W ; Barron, Martin J ; Borthwick, Gillian M ; Gospel, Amy ; Chinnery, Patrick F ; Samuels, David C ; Taylor, Geoffrey A ; Plusa, Stefan M ; Needham, Stephanie J ; Greaves, Laura C ; Kirkwood, Thomas B L ; Turnbull, Douglass M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3605-1ffcd1ae416f198c73be9a021091bb01f459bb76e4141d3e301d0539d61bb7043</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Aging</topic><topic>Bats</topic><topic>Biomedical research</topic><topic>Cancer</topic><topic>Colon - cytology</topic><topic>Colon - metabolism</topic><topic>Cytochrome</topic><topic>Dehydrogenases</topic><topic>Disease</topic><topic>DNA Replication</topic><topic>DNA, Mitochondrial - genetics</topic><topic>Electron Transport</topic><topic>Genomes</topic><topic>Humans</topic><topic>Mathematics</topic><topic>Middle Aged</topic><topic>Mitochondria</topic><topic>Mitochondrial DNA</topic><topic>Models, Genetic</topic><topic>Mutation</topic><topic>Phosphorylation</topic><topic>Proteins</topic><topic>Stem cells</topic><topic>Stem Cells - metabolism</topic><topic>Transfer RNA</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Taylor, Robert W</creatorcontrib><creatorcontrib>Barron, Martin J</creatorcontrib><creatorcontrib>Borthwick, Gillian M</creatorcontrib><creatorcontrib>Gospel, Amy</creatorcontrib><creatorcontrib>Chinnery, Patrick F</creatorcontrib><creatorcontrib>Samuels, David C</creatorcontrib><creatorcontrib>Taylor, Geoffrey A</creatorcontrib><creatorcontrib>Plusa, Stefan M</creatorcontrib><creatorcontrib>Needham, Stephanie J</creatorcontrib><creatorcontrib>Greaves, Laura C</creatorcontrib><creatorcontrib>Kirkwood, Thomas B L</creatorcontrib><creatorcontrib>Turnbull, Douglass M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing &amp; Allied Health Database</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>eLibrary</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of clinical investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Taylor, Robert W</au><au>Barron, Martin J</au><au>Borthwick, Gillian M</au><au>Gospel, Amy</au><au>Chinnery, Patrick F</au><au>Samuels, David C</au><au>Taylor, Geoffrey A</au><au>Plusa, Stefan M</au><au>Needham, Stephanie J</au><au>Greaves, Laura C</au><au>Kirkwood, Thomas B L</au><au>Turnbull, Douglass M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mitochondrial DNA mutations in human colonic crypt stem cells</atitle><jtitle>The Journal of clinical investigation</jtitle><addtitle>J Clin Invest</addtitle><date>2003-11</date><risdate>2003</risdate><volume>112</volume><issue>9</issue><spage>1351</spage><epage>1360</epage><pages>1351-1360</pages><issn>0021-9738</issn><eissn>1558-8238</eissn><abstract>The mitochondrial genome encodes 13 essential subunits of the respiratory chain and has remarkable genetics based on uniparental inheritance. Within human populations, the mitochondrial genome has a high rate of sequence divergence with multiple polymorphic variants and thus has played a major role in examining the evolutionary history of our species. In recent years it has also become apparent that pathogenic mitochondrial DNA (mtDNA) mutations play an important role in neurological and other diseases. Patients harbor many different mtDNA mutations, some of which are mtDNA mutations, some of which are inherited, but others that seem to be sporadic. It has also been suggested that mtDNA mutations play a role in aging and cancer, but the evidence for a causative role in these conditions is less clear. The accumulated data would suggest, however, that mtDNA mutations occur on a frequent basis. In this article we describe a new phenomenon: the accumulation of mtDNA mutations in human colonic crypt stem cells that result in a significant biochemical defect in their progeny. These studies have important consequences not only for understanding of the finding of mtDNA mutations in aging tissues and tumors, but also for determining the frequency of mtDNA mutations within a cell.</abstract><cop>United States</cop><pub>American Society for Clinical Investigation</pub><pmid>14597761</pmid><doi>10.1172/jci19435</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 0021-9738
ispartof The Journal of clinical investigation, 2003-11, Vol.112 (9), p.1351-1360
issn 0021-9738
1558-8238
language eng
recordid cdi_proquest_miscellaneous_71339962
source MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection
subjects Aged
Aged, 80 and over
Aging
Bats
Biomedical research
Cancer
Colon - cytology
Colon - metabolism
Cytochrome
Dehydrogenases
Disease
DNA Replication
DNA, Mitochondrial - genetics
Electron Transport
Genomes
Humans
Mathematics
Middle Aged
Mitochondria
Mitochondrial DNA
Models, Genetic
Mutation
Phosphorylation
Proteins
Stem cells
Stem Cells - metabolism
Transfer RNA
Tumors
title Mitochondrial DNA mutations in human colonic crypt stem cells
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-07T06%3A56%3A21IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Mitochondrial%20DNA%20mutations%20in%20human%20colonic%20crypt%20stem%20cells&rft.jtitle=The%20Journal%20of%20clinical%20investigation&rft.au=Taylor,%20Robert%20W&rft.date=2003-11&rft.volume=112&rft.issue=9&rft.spage=1351&rft.epage=1360&rft.pages=1351-1360&rft.issn=0021-9738&rft.eissn=1558-8238&rft_id=info:doi/10.1172/jci19435&rft_dat=%3Cproquest_cross%3E475759691%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=200516104&rft_id=info:pmid/14597761&rfr_iscdi=true