IronSulferCluV1, Main, Exploration, bibRecord, 000228

Mitochondrial lipoylation integrates age-associated decline in brown fat thermogenesis.

Identifieur interne : 000228 ( Main/Exploration ); précédent : 000227; suivant : 000229

Mitochondrial lipoylation integrates age-associated decline in brown fat thermogenesis.

Auteurs : Kazuki Tajima [États-Unis] ; Kenji Ikeda [États-Unis, Japon] ; Hsin-Yi Chang [Japon, Taïwan] ; Chih-Hsiang Chang [Japon] ; Takeshi Yoneshiro [États-Unis] ; Yasuo Oguri [États-Unis] ; Heejin Jun [États-Unis] ; Jun Wu [États-Unis] ; Yasushi Ishihama [Japon] ; Shingo Kajimura [États-Unis]

Source :

Nature metabolism [ 2522-5812 ] ; 2019.

RBID : pubmed:32313871

Abstract

Thermogenesis in brown adipose tissue (BAT) declines with age; however, what regulates this process remains poorly understood. Here, we identify mitochondria lipoylation as a previously unappreciated molecular hallmark of aged BAT in mice. Using mitochondrial proteomics, we show that mitochondrial lipoylation is disproportionally reduced in aged BAT through a post-transcriptional decrease in the iron-sulfur (Fe-S) cluster formation pathway. A defect in the Fe-S cluster formation by the fat-specific deletion of Bola3 significantly reduces mitochondrial lipoylation and fuel oxidation in BAT, leading to glucose intolerance and obesity. In turn, enhanced mitochondrial lipoylation by α-lipoic acid supplementation effectively restores BAT function in old mice, thereby preventing age-associated obesity and glucose intolerance. The effect of α-lipoic acids requires mitochondrial lipoylation via the Bola3 pathway and does not depend on the anti-oxidant activity of α-lipoic acid. These results open up the possibility to alleviate the age-associated decline in energy expenditure by enhancing the mitochondrial lipoylation pathway.

DOI: 10.1038/s42255-019-0106-z
PubMed: 32313871
PubMed Central: PMC7169975

Affiliations:

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<author><name sortKey="Oguri, Yasuo" sort="Oguri, Yasuo" uniqKey="Oguri Y" first="Yasuo" last="Oguri">Yasuo Oguri</name>
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<author><name sortKey="Tajima, Kazuki" sort="Tajima, Kazuki" uniqKey="Tajima K" first="Kazuki" last="Tajima">Kazuki Tajima</name>
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<author><name sortKey="Ikeda, Kenji" sort="Ikeda, Kenji" uniqKey="Ikeda K" first="Kenji" last="Ikeda">Kenji Ikeda</name>
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<author><name sortKey="Oguri, Yasuo" sort="Oguri, Yasuo" uniqKey="Oguri Y" first="Yasuo" last="Oguri">Yasuo Oguri</name>
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<author><name sortKey="Wu, Jun" sort="Wu, Jun" uniqKey="Wu J" first="Jun" last="Wu">Jun Wu</name>
<affiliation wicri:level="2"><nlm:affiliation>Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
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<affiliation wicri:level="2"><nlm:affiliation>Department of Molecular & Integrative Physiology, Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Molecular & Integrative Physiology, Life Sciences Institute, University of Michigan, Ann Arbor, MI</wicri:regionArea>
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<author><name sortKey="Ishihama, Yasushi" sort="Ishihama, Yasushi" uniqKey="Ishihama Y" first="Yasushi" last="Ishihama">Yasushi Ishihama</name>
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<country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Molecular and Cellular Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto</wicri:regionArea>
<orgName type="university">Université de Kyoto</orgName>
<placeName><settlement type="city">Kyoto</settlement>
<region type="prefecture">Région du Kansai</region>
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<author><name sortKey="Kajimura, Shingo" sort="Kajimura, Shingo" uniqKey="Kajimura S" first="Shingo" last="Kajimura">Shingo Kajimura</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>University of California, San Francisco Diabetes Center, San Francisco, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
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<affiliation wicri:level="2"><nlm:affiliation>Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, San Francisco, CA, USA. shingo.kajimura@ucsf.edu.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
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<placeName><region type="state">Californie</region>
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<affiliation wicri:level="2"><nlm:affiliation>Department of Cell and Tissue Biology, University of California, San Francisco, CA, USA. shingo.kajimura@ucsf.edu.</nlm:affiliation>
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<series><title level="j">Nature metabolism</title>
<idno type="eISSN">2522-5812</idno>
<imprint><date when="2019" type="published">2019</date>
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<front><div type="abstract" xml:lang="en">Thermogenesis in brown adipose tissue (BAT) declines with age; however, what regulates this process remains poorly understood. Here, we identify mitochondria lipoylation as a previously unappreciated molecular hallmark of aged BAT in mice. Using mitochondrial proteomics, we show that mitochondrial lipoylation is disproportionally reduced in aged BAT through a post-transcriptional decrease in the iron-sulfur (Fe-S) cluster formation pathway. A defect in the Fe-S cluster formation by the fat-specific deletion of <i>Bola3</i>
 significantly reduces mitochondrial lipoylation and fuel oxidation in BAT, leading to glucose intolerance and obesity. In turn, enhanced mitochondrial lipoylation by α-lipoic acid supplementation effectively restores BAT function in old mice, thereby preventing age-associated obesity and glucose intolerance. The effect of α-lipoic acids requires mitochondrial lipoylation <i>via</i>
 the Bola3 pathway and does not depend on the anti-oxidant activity of α-lipoic acid. These results open up the possibility to alleviate the age-associated decline in energy expenditure by enhancing the mitochondrial lipoylation pathway.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">32313871</PMID>
<DateRevised><Year>2020</Year>
<Month>09</Month>
<Day>15</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">2522-5812</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>1</Volume>
<Issue>9</Issue>
<PubDate><Year>2019</Year>
<Month>Sep</Month>
</PubDate>
</JournalIssue>
<Title>Nature metabolism</Title>
<ISOAbbreviation>Nat Metab</ISOAbbreviation>
</Journal>
<ArticleTitle>Mitochondrial lipoylation integrates age-associated decline in brown fat thermogenesis.</ArticleTitle>
<Pagination><MedlinePgn>886-898</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1038/s42255-019-0106-z</ELocationID>
<Abstract><AbstractText>Thermogenesis in brown adipose tissue (BAT) declines with age; however, what regulates this process remains poorly understood. Here, we identify mitochondria lipoylation as a previously unappreciated molecular hallmark of aged BAT in mice. Using mitochondrial proteomics, we show that mitochondrial lipoylation is disproportionally reduced in aged BAT through a post-transcriptional decrease in the iron-sulfur (Fe-S) cluster formation pathway. A defect in the Fe-S cluster formation by the fat-specific deletion of <i>Bola3</i>
 significantly reduces mitochondrial lipoylation and fuel oxidation in BAT, leading to glucose intolerance and obesity. In turn, enhanced mitochondrial lipoylation by α-lipoic acid supplementation effectively restores BAT function in old mice, thereby preventing age-associated obesity and glucose intolerance. The effect of α-lipoic acids requires mitochondrial lipoylation <i>via</i>
 the Bola3 pathway and does not depend on the anti-oxidant activity of α-lipoic acid. These results open up the possibility to alleviate the age-associated decline in energy expenditure by enhancing the mitochondrial lipoylation pathway.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Tajima</LastName>
<ForeName>Kazuki</ForeName>
<Initials>K</Initials>
<AffiliationInfo><Affiliation>University of California, San Francisco Diabetes Center, San Francisco, CA, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, San Francisco, CA, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Cell and Tissue Biology, University of California, San Francisco, CA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ikeda</LastName>
<ForeName>Kenji</ForeName>
<Initials>K</Initials>
<AffiliationInfo><Affiliation>University of California, San Francisco Diabetes Center, San Francisco, CA, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, San Francisco, CA, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Cell and Tissue Biology, University of California, San Francisco, CA, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Molecular Endocrionology and Metabolism, Tokyo Medical and Dental University, Tokyo, Japan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Chang</LastName>
<ForeName>Hsin-Yi</ForeName>
<Initials>HY</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0002-2742-0676</Identifier>
<AffiliationInfo><Affiliation>Department of Molecular and Cellular Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Graduate Institute of Metabolism and Obesity Sciences, Taipei Medical University, Taipei, Taiwan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Chang</LastName>
<ForeName>Chih-Hsiang</ForeName>
<Initials>CH</Initials>
<AffiliationInfo><Affiliation>Department of Molecular and Cellular Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Yoneshiro</LastName>
<ForeName>Takeshi</ForeName>
<Initials>T</Initials>
<AffiliationInfo><Affiliation>University of California, San Francisco Diabetes Center, San Francisco, CA, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, San Francisco, CA, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Cell and Tissue Biology, University of California, San Francisco, CA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Oguri</LastName>
<ForeName>Yasuo</ForeName>
<Initials>Y</Initials>
<AffiliationInfo><Affiliation>University of California, San Francisco Diabetes Center, San Francisco, CA, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, San Francisco, CA, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Cell and Tissue Biology, University of California, San Francisco, CA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Jun</LastName>
<ForeName>Heejin</ForeName>
<Initials>H</Initials>
<AffiliationInfo><Affiliation>Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Wu</LastName>
<ForeName>Jun</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Molecular & Integrative Physiology, Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Ishihama</LastName>
<ForeName>Yasushi</ForeName>
<Initials>Y</Initials>
<AffiliationInfo><Affiliation>Department of Molecular and Cellular Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kajimura</LastName>
<ForeName>Shingo</ForeName>
<Initials>S</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0003-0672-5910</Identifier>
<AffiliationInfo><Affiliation>University of California, San Francisco Diabetes Center, San Francisco, CA, USA. shingo.kajimura@ucsf.edu.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, San Francisco, CA, USA. shingo.kajimura@ucsf.edu.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Department of Cell and Tissue Biology, University of California, San Francisco, CA, USA. shingo.kajimura@ucsf.edu.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<GrantList CompleteYN="Y"><Grant><GrantID>R01 DK097441</GrantID>
<Acronym>DK</Acronym>
<Agency>NIDDK NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>R01 DK107583</GrantID>
<Acronym>DK</Acronym>
<Agency>NIDDK NIH HHS</Agency>
<Country>United States</Country>
</Grant>
<Grant><GrantID>R01 DK108822</GrantID>
<Acronym>DK</Acronym>
<Agency>NIDDK NIH HHS</Agency>
<Country>United States</Country>
</Grant>
</GrantList>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2019</Year>
<Month>09</Month>
<Day>16</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>Germany</Country>
<MedlineTA>Nat Metab</MedlineTA>
<NlmUniqueID>101736592</NlmUniqueID>
<ISSNLinking>2522-5812</ISSNLinking>
</MedlineJournalInfo>
<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Brown adipose tissue</Keyword>
<Keyword MajorTopicYN="N">Glucose metabolism</Keyword>
<Keyword MajorTopicYN="N">Mitochondria</Keyword>
<Keyword MajorTopicYN="N">Thermogenesis</Keyword>
</KeywordList>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2020</Year>
<Month>4</Month>
<Day>22</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed"><Year>2020</Year>
<Month>4</Month>
<Day>22</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline"><Year>2020</Year>
<Month>4</Month>
<Day>22</Day>
<Hour>6</Hour>
<Minute>1</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>ppublish</PublicationStatus>
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<ArticleId IdType="doi">10.1038/s42255-019-0106-z</ArticleId>
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<affiliations><list><country><li>Japon</li>
<li>Taïwan</li>
<li>États-Unis</li>
</country>
<region><li>Californie</li>
<li>Michigan</li>
<li>Région de Kantō</li>
<li>Région du Kansai</li>
</region>
<settlement><li>Kyoto</li>
<li>Tokyo</li>
</settlement>
<orgName><li>Université de Kyoto</li>
</orgName>
</list>
<tree><country name="États-Unis"><region name="Californie"><name sortKey="Tajima, Kazuki" sort="Tajima, Kazuki" uniqKey="Tajima K" first="Kazuki" last="Tajima">Kazuki Tajima</name>
</region>
<name sortKey="Ikeda, Kenji" sort="Ikeda, Kenji" uniqKey="Ikeda K" first="Kenji" last="Ikeda">Kenji Ikeda</name>
<name sortKey="Ikeda, Kenji" sort="Ikeda, Kenji" uniqKey="Ikeda K" first="Kenji" last="Ikeda">Kenji Ikeda</name>
<name sortKey="Ikeda, Kenji" sort="Ikeda, Kenji" uniqKey="Ikeda K" first="Kenji" last="Ikeda">Kenji Ikeda</name>
<name sortKey="Jun, Heejin" sort="Jun, Heejin" uniqKey="Jun H" first="Heejin" last="Jun">Heejin Jun</name>
<name sortKey="Kajimura, Shingo" sort="Kajimura, Shingo" uniqKey="Kajimura S" first="Shingo" last="Kajimura">Shingo Kajimura</name>
<name sortKey="Kajimura, Shingo" sort="Kajimura, Shingo" uniqKey="Kajimura S" first="Shingo" last="Kajimura">Shingo Kajimura</name>
<name sortKey="Kajimura, Shingo" sort="Kajimura, Shingo" uniqKey="Kajimura S" first="Shingo" last="Kajimura">Shingo Kajimura</name>
<name sortKey="Oguri, Yasuo" sort="Oguri, Yasuo" uniqKey="Oguri Y" first="Yasuo" last="Oguri">Yasuo Oguri</name>
<name sortKey="Oguri, Yasuo" sort="Oguri, Yasuo" uniqKey="Oguri Y" first="Yasuo" last="Oguri">Yasuo Oguri</name>
<name sortKey="Oguri, Yasuo" sort="Oguri, Yasuo" uniqKey="Oguri Y" first="Yasuo" last="Oguri">Yasuo Oguri</name>
<name sortKey="Tajima, Kazuki" sort="Tajima, Kazuki" uniqKey="Tajima K" first="Kazuki" last="Tajima">Kazuki Tajima</name>
<name sortKey="Tajima, Kazuki" sort="Tajima, Kazuki" uniqKey="Tajima K" first="Kazuki" last="Tajima">Kazuki Tajima</name>
<name sortKey="Wu, Jun" sort="Wu, Jun" uniqKey="Wu J" first="Jun" last="Wu">Jun Wu</name>
<name sortKey="Wu, Jun" sort="Wu, Jun" uniqKey="Wu J" first="Jun" last="Wu">Jun Wu</name>
<name sortKey="Yoneshiro, Takeshi" sort="Yoneshiro, Takeshi" uniqKey="Yoneshiro T" first="Takeshi" last="Yoneshiro">Takeshi Yoneshiro</name>
<name sortKey="Yoneshiro, Takeshi" sort="Yoneshiro, Takeshi" uniqKey="Yoneshiro T" first="Takeshi" last="Yoneshiro">Takeshi Yoneshiro</name>
<name sortKey="Yoneshiro, Takeshi" sort="Yoneshiro, Takeshi" uniqKey="Yoneshiro T" first="Takeshi" last="Yoneshiro">Takeshi Yoneshiro</name>
</country>
<country name="Japon"><region name="Région de Kantō"><name sortKey="Ikeda, Kenji" sort="Ikeda, Kenji" uniqKey="Ikeda K" first="Kenji" last="Ikeda">Kenji Ikeda</name>
</region>
<name sortKey="Chang, Chih Hsiang" sort="Chang, Chih Hsiang" uniqKey="Chang C" first="Chih-Hsiang" last="Chang">Chih-Hsiang Chang</name>
<name sortKey="Chang, Hsin Yi" sort="Chang, Hsin Yi" uniqKey="Chang H" first="Hsin-Yi" last="Chang">Hsin-Yi Chang</name>
<name sortKey="Ishihama, Yasushi" sort="Ishihama, Yasushi" uniqKey="Ishihama Y" first="Yasushi" last="Ishihama">Yasushi Ishihama</name>
</country>
<country name="Taïwan"><noRegion><name sortKey="Chang, Hsin Yi" sort="Chang, Hsin Yi" uniqKey="Chang H" first="Hsin-Yi" last="Chang">Hsin-Yi Chang</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>

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Mitochondrial lipoylation integrates age-associated decline in brown fat thermogenesis.

Mitochondrial lipoylation integrates age-associated decline in brown fat thermogenesis.

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