UPR ER promotes lipophagy independent of chaperones to extend life span
Longevity is dictated by a combination of environmental and genetic factors. One of the key mechanisms to regulate life-span extension is the induction of protein chaperones for protein homeostasis. Ectopic activation of the unfolded protein response of the endoplasmic reticulum (UPR ) specifically...
Gespeichert in:
| Veröffentlicht in: | Science advances 2020-01, Vol.6 (1), p.eaaz1441 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 1 |
| container_start_page | eaaz1441 |
| container_title | Science advances |
| container_volume | 6 |
| creator | Daniele, Joseph R Higuchi-Sanabria, Ryo Durieux, Jenni Monshietehadi, Samira Ramachandran, Vidhya Tronnes, Sarah U Kelet, Naame Sanchez, Melissa Metcalf, Melissa G Garcia, Gilberto Frankino, Phillip A Benitez, Camila Zeng, Mandy Esping, Daniel J Joe, Larry Dillin, Andrew |
| description | Longevity is dictated by a combination of environmental and genetic factors. One of the key mechanisms to regulate life-span extension is the induction of protein chaperones for protein homeostasis. Ectopic activation of the unfolded protein response of the endoplasmic reticulum (UPR
) specifically in neurons is sufficient to enhance organismal stress resistance and extend life span. Here, we find that this activation not only promotes chaperones but also facilitates ER restructuring and ER function. This restructuring is concomitant with lipid depletion through lipophagy. Activation of lipophagy is distinct from chaperone induction and is required for the life-span extension found in this paradigm. Last, we find that overexpression of the lipophagy component,
, is sufficient to deplete lipids, remodel ER, and promote life span. Therefore, UPR induction in neurons triggers two distinct programs in the periphery: the proteostasis arm through protein chaperones and metabolic changes through lipid depletion mediated by EH domain binding protein 1 (EHBP-1). |
| doi_str_mv | 10.1126/sciadv.aaz1441 |
| format | Article |
| fullrecord | <record><control><sourceid>pubmed_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1126_sciadv_aaz1441</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>31911951</sourcerecordid><originalsourceid>FETCH-LOGICAL-c1471-82e1a1a82813286ba69db5bb57ce0e2d56858412c0ea5a59b0ef2806f253d2263</originalsourceid><addsrcrecordid>eNpNkMFKw0AQhhdRbKm9epR9gcSdTXazOUqpVSgoxZ7DJJm1kTa7ZKNYn95IqniZGfi_fw4fY9cgYgCpb0PVYP0RI35BmsIZm8okU5FUqTn_d0_YPIQ3IQSkWivIL9kkgRwgVzBlq-3zhi833Hfu4HoKfN9453f4euRNW5OnYbQ9d5ZXO_TUuXZgesfpsx-igbbEg8f2il1Y3Aean_aMbe-XL4uHaP20elzcraMK0gwiIwkQ0EgDiTS6RJ3XpSpLlVUkSNZKG2VSkJUgVKjyUpCVRmgrVVJLqZMZi8e_VedC6MgWvmsO2B0LEMWPlGKUUpykDIWbseDfywPVf_ivguQbLiheiQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>UPR ER promotes lipophagy independent of chaperones to extend life span</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Daniele, Joseph R ; Higuchi-Sanabria, Ryo ; Durieux, Jenni ; Monshietehadi, Samira ; Ramachandran, Vidhya ; Tronnes, Sarah U ; Kelet, Naame ; Sanchez, Melissa ; Metcalf, Melissa G ; Garcia, Gilberto ; Frankino, Phillip A ; Benitez, Camila ; Zeng, Mandy ; Esping, Daniel J ; Joe, Larry ; Dillin, Andrew</creator><creatorcontrib>Daniele, Joseph R ; Higuchi-Sanabria, Ryo ; Durieux, Jenni ; Monshietehadi, Samira ; Ramachandran, Vidhya ; Tronnes, Sarah U ; Kelet, Naame ; Sanchez, Melissa ; Metcalf, Melissa G ; Garcia, Gilberto ; Frankino, Phillip A ; Benitez, Camila ; Zeng, Mandy ; Esping, Daniel J ; Joe, Larry ; Dillin, Andrew</creatorcontrib><description>Longevity is dictated by a combination of environmental and genetic factors. One of the key mechanisms to regulate life-span extension is the induction of protein chaperones for protein homeostasis. Ectopic activation of the unfolded protein response of the endoplasmic reticulum (UPR
) specifically in neurons is sufficient to enhance organismal stress resistance and extend life span. Here, we find that this activation not only promotes chaperones but also facilitates ER restructuring and ER function. This restructuring is concomitant with lipid depletion through lipophagy. Activation of lipophagy is distinct from chaperone induction and is required for the life-span extension found in this paradigm. Last, we find that overexpression of the lipophagy component,
, is sufficient to deplete lipids, remodel ER, and promote life span. Therefore, UPR induction in neurons triggers two distinct programs in the periphery: the proteostasis arm through protein chaperones and metabolic changes through lipid depletion mediated by EH domain binding protein 1 (EHBP-1).</description><identifier>ISSN: 2375-2548</identifier><identifier>EISSN: 2375-2548</identifier><identifier>DOI: 10.1126/sciadv.aaz1441</identifier><identifier>PMID: 31911951</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Autophagy - genetics ; Caenorhabditis elegans ; Caenorhabditis elegans Proteins - genetics ; Endoplasmic Reticulum - genetics ; Endoplasmic Reticulum Stress - genetics ; Humans ; Lipids - genetics ; Longevity - genetics ; Molecular Chaperones - genetics ; Neurons - metabolism ; Signal Transduction - genetics ; Unfolded Protein Response - genetics ; Vesicular Transport Proteins - genetics</subject><ispartof>Science advances, 2020-01, Vol.6 (1), p.eaaz1441</ispartof><rights>Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c1471-82e1a1a82813286ba69db5bb57ce0e2d56858412c0ea5a59b0ef2806f253d2263</citedby><cites>FETCH-LOGICAL-c1471-82e1a1a82813286ba69db5bb57ce0e2d56858412c0ea5a59b0ef2806f253d2263</cites><orcidid>0000-0001-7061-2975 ; 0000-0003-2030-5656 ; 0000-0002-4403-3977 ; 0000-0002-2462-821X ; 0000-0002-7427-2629 ; 0000-0001-8936-5812 ; 0000-0001-5357-046X ; 0000-0001-8651-7307 ; 0000-0002-3909-3422</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,864,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31911951$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Daniele, Joseph R</creatorcontrib><creatorcontrib>Higuchi-Sanabria, Ryo</creatorcontrib><creatorcontrib>Durieux, Jenni</creatorcontrib><creatorcontrib>Monshietehadi, Samira</creatorcontrib><creatorcontrib>Ramachandran, Vidhya</creatorcontrib><creatorcontrib>Tronnes, Sarah U</creatorcontrib><creatorcontrib>Kelet, Naame</creatorcontrib><creatorcontrib>Sanchez, Melissa</creatorcontrib><creatorcontrib>Metcalf, Melissa G</creatorcontrib><creatorcontrib>Garcia, Gilberto</creatorcontrib><creatorcontrib>Frankino, Phillip A</creatorcontrib><creatorcontrib>Benitez, Camila</creatorcontrib><creatorcontrib>Zeng, Mandy</creatorcontrib><creatorcontrib>Esping, Daniel J</creatorcontrib><creatorcontrib>Joe, Larry</creatorcontrib><creatorcontrib>Dillin, Andrew</creatorcontrib><title>UPR ER promotes lipophagy independent of chaperones to extend life span</title><title>Science advances</title><addtitle>Sci Adv</addtitle><description>Longevity is dictated by a combination of environmental and genetic factors. One of the key mechanisms to regulate life-span extension is the induction of protein chaperones for protein homeostasis. Ectopic activation of the unfolded protein response of the endoplasmic reticulum (UPR
) specifically in neurons is sufficient to enhance organismal stress resistance and extend life span. Here, we find that this activation not only promotes chaperones but also facilitates ER restructuring and ER function. This restructuring is concomitant with lipid depletion through lipophagy. Activation of lipophagy is distinct from chaperone induction and is required for the life-span extension found in this paradigm. Last, we find that overexpression of the lipophagy component,
, is sufficient to deplete lipids, remodel ER, and promote life span. Therefore, UPR induction in neurons triggers two distinct programs in the periphery: the proteostasis arm through protein chaperones and metabolic changes through lipid depletion mediated by EH domain binding protein 1 (EHBP-1).</description><subject>Animals</subject><subject>Autophagy - genetics</subject><subject>Caenorhabditis elegans</subject><subject>Caenorhabditis elegans Proteins - genetics</subject><subject>Endoplasmic Reticulum - genetics</subject><subject>Endoplasmic Reticulum Stress - genetics</subject><subject>Humans</subject><subject>Lipids - genetics</subject><subject>Longevity - genetics</subject><subject>Molecular Chaperones - genetics</subject><subject>Neurons - metabolism</subject><subject>Signal Transduction - genetics</subject><subject>Unfolded Protein Response - genetics</subject><subject>Vesicular Transport Proteins - genetics</subject><issn>2375-2548</issn><issn>2375-2548</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkMFKw0AQhhdRbKm9epR9gcSdTXazOUqpVSgoxZ7DJJm1kTa7ZKNYn95IqniZGfi_fw4fY9cgYgCpb0PVYP0RI35BmsIZm8okU5FUqTn_d0_YPIQ3IQSkWivIL9kkgRwgVzBlq-3zhi833Hfu4HoKfN9453f4euRNW5OnYbQ9d5ZXO_TUuXZgesfpsx-igbbEg8f2il1Y3Aean_aMbe-XL4uHaP20elzcraMK0gwiIwkQ0EgDiTS6RJ3XpSpLlVUkSNZKG2VSkJUgVKjyUpCVRmgrVVJLqZMZi8e_VedC6MgWvmsO2B0LEMWPlGKUUpykDIWbseDfywPVf_ivguQbLiheiQ</recordid><startdate>20200103</startdate><enddate>20200103</enddate><creator>Daniele, Joseph R</creator><creator>Higuchi-Sanabria, Ryo</creator><creator>Durieux, Jenni</creator><creator>Monshietehadi, Samira</creator><creator>Ramachandran, Vidhya</creator><creator>Tronnes, Sarah U</creator><creator>Kelet, Naame</creator><creator>Sanchez, Melissa</creator><creator>Metcalf, Melissa G</creator><creator>Garcia, Gilberto</creator><creator>Frankino, Phillip A</creator><creator>Benitez, Camila</creator><creator>Zeng, Mandy</creator><creator>Esping, Daniel J</creator><creator>Joe, Larry</creator><creator>Dillin, Andrew</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><orcidid>https://orcid.org/0000-0001-7061-2975</orcidid><orcidid>https://orcid.org/0000-0003-2030-5656</orcidid><orcidid>https://orcid.org/0000-0002-4403-3977</orcidid><orcidid>https://orcid.org/0000-0002-2462-821X</orcidid><orcidid>https://orcid.org/0000-0002-7427-2629</orcidid><orcidid>https://orcid.org/0000-0001-8936-5812</orcidid><orcidid>https://orcid.org/0000-0001-5357-046X</orcidid><orcidid>https://orcid.org/0000-0001-8651-7307</orcidid><orcidid>https://orcid.org/0000-0002-3909-3422</orcidid></search><sort><creationdate>20200103</creationdate><title>UPR ER promotes lipophagy independent of chaperones to extend life span</title><author>Daniele, Joseph R ; Higuchi-Sanabria, Ryo ; Durieux, Jenni ; Monshietehadi, Samira ; Ramachandran, Vidhya ; Tronnes, Sarah U ; Kelet, Naame ; Sanchez, Melissa ; Metcalf, Melissa G ; Garcia, Gilberto ; Frankino, Phillip A ; Benitez, Camila ; Zeng, Mandy ; Esping, Daniel J ; Joe, Larry ; Dillin, Andrew</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1471-82e1a1a82813286ba69db5bb57ce0e2d56858412c0ea5a59b0ef2806f253d2263</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Autophagy - genetics</topic><topic>Caenorhabditis elegans</topic><topic>Caenorhabditis elegans Proteins - genetics</topic><topic>Endoplasmic Reticulum - genetics</topic><topic>Endoplasmic Reticulum Stress - genetics</topic><topic>Humans</topic><topic>Lipids - genetics</topic><topic>Longevity - genetics</topic><topic>Molecular Chaperones - genetics</topic><topic>Neurons - metabolism</topic><topic>Signal Transduction - genetics</topic><topic>Unfolded Protein Response - genetics</topic><topic>Vesicular Transport Proteins - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Daniele, Joseph R</creatorcontrib><creatorcontrib>Higuchi-Sanabria, Ryo</creatorcontrib><creatorcontrib>Durieux, Jenni</creatorcontrib><creatorcontrib>Monshietehadi, Samira</creatorcontrib><creatorcontrib>Ramachandran, Vidhya</creatorcontrib><creatorcontrib>Tronnes, Sarah U</creatorcontrib><creatorcontrib>Kelet, Naame</creatorcontrib><creatorcontrib>Sanchez, Melissa</creatorcontrib><creatorcontrib>Metcalf, Melissa G</creatorcontrib><creatorcontrib>Garcia, Gilberto</creatorcontrib><creatorcontrib>Frankino, Phillip A</creatorcontrib><creatorcontrib>Benitez, Camila</creatorcontrib><creatorcontrib>Zeng, Mandy</creatorcontrib><creatorcontrib>Esping, Daniel J</creatorcontrib><creatorcontrib>Joe, Larry</creatorcontrib><creatorcontrib>Dillin, Andrew</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Science advances</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Daniele, Joseph R</au><au>Higuchi-Sanabria, Ryo</au><au>Durieux, Jenni</au><au>Monshietehadi, Samira</au><au>Ramachandran, Vidhya</au><au>Tronnes, Sarah U</au><au>Kelet, Naame</au><au>Sanchez, Melissa</au><au>Metcalf, Melissa G</au><au>Garcia, Gilberto</au><au>Frankino, Phillip A</au><au>Benitez, Camila</au><au>Zeng, Mandy</au><au>Esping, Daniel J</au><au>Joe, Larry</au><au>Dillin, Andrew</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>UPR ER promotes lipophagy independent of chaperones to extend life span</atitle><jtitle>Science advances</jtitle><addtitle>Sci Adv</addtitle><date>2020-01-03</date><risdate>2020</risdate><volume>6</volume><issue>1</issue><spage>eaaz1441</spage><pages>eaaz1441-</pages><issn>2375-2548</issn><eissn>2375-2548</eissn><abstract>Longevity is dictated by a combination of environmental and genetic factors. One of the key mechanisms to regulate life-span extension is the induction of protein chaperones for protein homeostasis. Ectopic activation of the unfolded protein response of the endoplasmic reticulum (UPR
) specifically in neurons is sufficient to enhance organismal stress resistance and extend life span. Here, we find that this activation not only promotes chaperones but also facilitates ER restructuring and ER function. This restructuring is concomitant with lipid depletion through lipophagy. Activation of lipophagy is distinct from chaperone induction and is required for the life-span extension found in this paradigm. Last, we find that overexpression of the lipophagy component,
, is sufficient to deplete lipids, remodel ER, and promote life span. Therefore, UPR induction in neurons triggers two distinct programs in the periphery: the proteostasis arm through protein chaperones and metabolic changes through lipid depletion mediated by EH domain binding protein 1 (EHBP-1).</abstract><cop>United States</cop><pmid>31911951</pmid><doi>10.1126/sciadv.aaz1441</doi><orcidid>https://orcid.org/0000-0001-7061-2975</orcidid><orcidid>https://orcid.org/0000-0003-2030-5656</orcidid><orcidid>https://orcid.org/0000-0002-4403-3977</orcidid><orcidid>https://orcid.org/0000-0002-2462-821X</orcidid><orcidid>https://orcid.org/0000-0002-7427-2629</orcidid><orcidid>https://orcid.org/0000-0001-8936-5812</orcidid><orcidid>https://orcid.org/0000-0001-5357-046X</orcidid><orcidid>https://orcid.org/0000-0001-8651-7307</orcidid><orcidid>https://orcid.org/0000-0002-3909-3422</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2375-2548 |
| ispartof | Science advances, 2020-01, Vol.6 (1), p.eaaz1441 |
| issn | 2375-2548 2375-2548 |
| language | eng |
| recordid | cdi_crossref_primary_10_1126_sciadv_aaz1441 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Animals Autophagy - genetics Caenorhabditis elegans Caenorhabditis elegans Proteins - genetics Endoplasmic Reticulum - genetics Endoplasmic Reticulum Stress - genetics Humans Lipids - genetics Longevity - genetics Molecular Chaperones - genetics Neurons - metabolism Signal Transduction - genetics Unfolded Protein Response - genetics Vesicular Transport Proteins - genetics |
| title | UPR ER promotes lipophagy independent of chaperones to extend life span |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-06T11%3A13%3A40IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-pubmed_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=UPR%20ER%20promotes%20lipophagy%20independent%20of%20chaperones%20to%20extend%20life%20span&rft.jtitle=Science%20advances&rft.au=Daniele,%20Joseph%20R&rft.date=2020-01-03&rft.volume=6&rft.issue=1&rft.spage=eaaz1441&rft.pages=eaaz1441-&rft.issn=2375-2548&rft.eissn=2375-2548&rft_id=info:doi/10.1126/sciadv.aaz1441&rft_dat=%3Cpubmed_cross%3E31911951%3C/pubmed_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/31911951&rfr_iscdi=true |