FUNDC1 regulates mitochondrial dynamics at the ER-mitochondrial contact site under hypoxic conditions
In hypoxic cells, dysfunctional mitochondria are selectively removed by a specialized autophagic process called mitophagy. The ER–mitochondrial contact site (MAM) is essential for fission of mitochondria prior to engulfment, and the outer mitochondrial membrane protein FUNDC1 interacts with LC3 to r...
Gespeichert in:
Veröffentlicht in: | The EMBO journal 2016-07, Vol.35 (13), p.1368-1384 |
---|---|
Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext bestellen |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 1384 |
---|---|
container_issue | 13 |
container_start_page | 1368 |
container_title | The EMBO journal |
container_volume | 35 |
creator | Wu, Wenxian Lin, Chunxia Wu, Keng Jiang, Lei Wang, Xiaojing Li, Wen Zhuang, Haixia Zhang, Xingliang Chen, Hao Li, Shupeng Yang, Yue Lu, Yue Wang, Jingjing Zhu, Runzhi Zhang, Liangqing Sui, Senfang Tan, Ning Zhao, Bin Zhang, Jingjing Li, Longxuan Feng, Du |
description | In hypoxic cells, dysfunctional mitochondria are selectively removed by a specialized autophagic process called mitophagy. The ER–mitochondrial contact site (MAM) is essential for fission of mitochondria prior to engulfment, and the outer mitochondrial membrane protein FUNDC1 interacts with LC3 to recruit autophagosomes, but the mechanisms integrating these processes are poorly understood. Here, we describe a new pathway mediating mitochondrial fission and subsequent mitophagy under hypoxic conditions. FUNDC1 accumulates at the MAM by associating with the ER membrane protein calnexin. As mitophagy proceeds, FUNDC1/calnexin association attenuates and the exposed cytosolic loop of FUNDC1 interacts with DRP1 instead. DRP1 is thereby recruited to the MAM, and mitochondrial fission then occurs. Knockdown of FUNDC1, DRP1, or calnexin prevents fission and mitophagy under hypoxic conditions. Thus, FUNDC1 integrates mitochondrial fission and mitophagy at the interface of the MAM by working in concert with DRP1 and calnexin under hypoxic conditions in mammalian cells.
Synopsis
In response to hypoxia, mitophagy receptor FUNDC1 associates with ER‐resident protein calnexin and thereby accumulates at the ER–mitochondrial contact site; this allows for DRP‐1 recruitment and thus mitochondrial fission.
FUNDC1 accumulates at the ER–mitochondrial contact site (MAM) by association with calnexin in response to hypoxia.
FUNDC1 mediates mitochondrial fission in response to hypoxia.
FUNDC1 binds to DRP1 for mitochondrial fission during hypoxia.
FUNDC1 is the molecular link that integrates mitochondrial fission and mitophagy at the interface of the MAM.
Graphical Abstract
In response to hypoxia, mitophagy receptor FUNDC1 associates with ER‐resident protein calnexin and thereby accumulates at the ER–mitochondrial contact site; this allows for DRP‐1 recruitment and thus mitochondrial fission. |
doi_str_mv | 10.15252/embj.201593102 |
format | Article |
fullrecord | <record><control><sourceid>proquest_C6C</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4864280</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>4106970461</sourcerecordid><originalsourceid>FETCH-LOGICAL-i5642-3cbf9c0533d4b5ffd3ef7d4c846a10340cc55335babdbece5e9b1d65188c57c43</originalsourceid><addsrcrecordid>eNptkc1uEzEUhS0EoqGwZodGYsNmin9nHBZIbUhTqlKkigp2lsf2JA4zdrA9bfM2PAtPhmnKqEWsLOt859x7dQB4ieABYpjht6Zv1gcYIjYlCOJHYIJoBUsMa_YYTCCuUEkRn-6BZzGuIYSM1-gp2MM1otlBJqA9vjz_MENFMMuhk8nEorfJq5V3OljZFXrrZG9VLGQq0soU84vyIaC8S1KlItpkisFpE4rVduNvrPr1M2vaJutdfA6etLKL5sXduw8uj-dfZifl2efFx9nhWWlZRXFJVNNOFWSEaNqwttXEtLWmitNKIkgoVIplkTWy0Y1Rhplpg3TFEOeK1YqSffB-l7sZmt5oZVwKshObYHsZtsJLKx4qzq7E0l8JyvN8DnPAm7uA4H8MJibR26hM10ln_BAF4hBRQjkhGX39D7r2Q3D5vFuKcIJrlqlX9zcaV_lbQQbe7YBr25ntqCMobhsWfxoWY8Ni_unodPxlM9yZY_a5pQn3dvh_QLaUO4uNydyM82T4Lqqa1Ex8PV-Ii4rg06PFifhGfgMyvLuZ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1801383275</pqid></control><display><type>article</type><title>FUNDC1 regulates mitochondrial dynamics at the ER-mitochondrial contact site under hypoxic conditions</title><source>Springer Nature OA/Free Journals</source><creator>Wu, Wenxian ; Lin, Chunxia ; Wu, Keng ; Jiang, Lei ; Wang, Xiaojing ; Li, Wen ; Zhuang, Haixia ; Zhang, Xingliang ; Chen, Hao ; Li, Shupeng ; Yang, Yue ; Lu, Yue ; Wang, Jingjing ; Zhu, Runzhi ; Zhang, Liangqing ; Sui, Senfang ; Tan, Ning ; Zhao, Bin ; Zhang, Jingjing ; Li, Longxuan ; Feng, Du</creator><creatorcontrib>Wu, Wenxian ; Lin, Chunxia ; Wu, Keng ; Jiang, Lei ; Wang, Xiaojing ; Li, Wen ; Zhuang, Haixia ; Zhang, Xingliang ; Chen, Hao ; Li, Shupeng ; Yang, Yue ; Lu, Yue ; Wang, Jingjing ; Zhu, Runzhi ; Zhang, Liangqing ; Sui, Senfang ; Tan, Ning ; Zhao, Bin ; Zhang, Jingjing ; Li, Longxuan ; Feng, Du</creatorcontrib><description>In hypoxic cells, dysfunctional mitochondria are selectively removed by a specialized autophagic process called mitophagy. The ER–mitochondrial contact site (MAM) is essential for fission of mitochondria prior to engulfment, and the outer mitochondrial membrane protein FUNDC1 interacts with LC3 to recruit autophagosomes, but the mechanisms integrating these processes are poorly understood. Here, we describe a new pathway mediating mitochondrial fission and subsequent mitophagy under hypoxic conditions. FUNDC1 accumulates at the MAM by associating with the ER membrane protein calnexin. As mitophagy proceeds, FUNDC1/calnexin association attenuates and the exposed cytosolic loop of FUNDC1 interacts with DRP1 instead. DRP1 is thereby recruited to the MAM, and mitochondrial fission then occurs. Knockdown of FUNDC1, DRP1, or calnexin prevents fission and mitophagy under hypoxic conditions. Thus, FUNDC1 integrates mitochondrial fission and mitophagy at the interface of the MAM by working in concert with DRP1 and calnexin under hypoxic conditions in mammalian cells.
Synopsis
In response to hypoxia, mitophagy receptor FUNDC1 associates with ER‐resident protein calnexin and thereby accumulates at the ER–mitochondrial contact site; this allows for DRP‐1 recruitment and thus mitochondrial fission.
FUNDC1 accumulates at the ER–mitochondrial contact site (MAM) by association with calnexin in response to hypoxia.
FUNDC1 mediates mitochondrial fission in response to hypoxia.
FUNDC1 binds to DRP1 for mitochondrial fission during hypoxia.
FUNDC1 is the molecular link that integrates mitochondrial fission and mitophagy at the interface of the MAM.
Graphical Abstract
In response to hypoxia, mitophagy receptor FUNDC1 associates with ER‐resident protein calnexin and thereby accumulates at the ER–mitochondrial contact site; this allows for DRP‐1 recruitment and thus mitochondrial fission.</description><identifier>ISSN: 0261-4189</identifier><identifier>EISSN: 1460-2075</identifier><identifier>DOI: 10.15252/embj.201593102</identifier><identifier>PMID: 27145933</identifier><identifier>CODEN: EMJODG</identifier><language>eng</language><publisher>London: Blackwell Publishing Ltd</publisher><subject>autophagy ; Calnexin - metabolism ; Cells, Cultured ; Cellular biology ; Dynamins ; EMBO07 ; EMBO20 ; EMBO21 ; Endoplasmic Reticulum - metabolism ; ER-mitochondrial contact site ; GTP Phosphohydrolases - metabolism ; Humans ; Hypoxia ; MAM ; Membrane Proteins - metabolism ; Microtubule-Associated Proteins - metabolism ; Mitochondria ; Mitochondrial Dynamics ; mitochondrial fission ; Mitochondrial Proteins - metabolism ; Mitophagy ; Protein Binding ; Proteins</subject><ispartof>The EMBO journal, 2016-07, Vol.35 (13), p.1368-1384</ispartof><rights>The Authors 2016</rights><rights>2016 The Authors</rights><rights>2016 The Authors.</rights><rights>2016 EMBO</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0002-2489-4702</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4864280/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4864280/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,315,729,782,786,887,1419,1435,27931,27932,41127,42196,45581,45582,46416,46840,51583,53798,53800</link.rule.ids><linktorsrc>$$Uhttps://doi.org/10.15252/embj.201593102$$EView_record_in_Springer_Nature$$FView_record_in_$$GSpringer_Nature</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27145933$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Wenxian</creatorcontrib><creatorcontrib>Lin, Chunxia</creatorcontrib><creatorcontrib>Wu, Keng</creatorcontrib><creatorcontrib>Jiang, Lei</creatorcontrib><creatorcontrib>Wang, Xiaojing</creatorcontrib><creatorcontrib>Li, Wen</creatorcontrib><creatorcontrib>Zhuang, Haixia</creatorcontrib><creatorcontrib>Zhang, Xingliang</creatorcontrib><creatorcontrib>Chen, Hao</creatorcontrib><creatorcontrib>Li, Shupeng</creatorcontrib><creatorcontrib>Yang, Yue</creatorcontrib><creatorcontrib>Lu, Yue</creatorcontrib><creatorcontrib>Wang, Jingjing</creatorcontrib><creatorcontrib>Zhu, Runzhi</creatorcontrib><creatorcontrib>Zhang, Liangqing</creatorcontrib><creatorcontrib>Sui, Senfang</creatorcontrib><creatorcontrib>Tan, Ning</creatorcontrib><creatorcontrib>Zhao, Bin</creatorcontrib><creatorcontrib>Zhang, Jingjing</creatorcontrib><creatorcontrib>Li, Longxuan</creatorcontrib><creatorcontrib>Feng, Du</creatorcontrib><title>FUNDC1 regulates mitochondrial dynamics at the ER-mitochondrial contact site under hypoxic conditions</title><title>The EMBO journal</title><addtitle>EMBO J</addtitle><addtitle>EMBO J</addtitle><description>In hypoxic cells, dysfunctional mitochondria are selectively removed by a specialized autophagic process called mitophagy. The ER–mitochondrial contact site (MAM) is essential for fission of mitochondria prior to engulfment, and the outer mitochondrial membrane protein FUNDC1 interacts with LC3 to recruit autophagosomes, but the mechanisms integrating these processes are poorly understood. Here, we describe a new pathway mediating mitochondrial fission and subsequent mitophagy under hypoxic conditions. FUNDC1 accumulates at the MAM by associating with the ER membrane protein calnexin. As mitophagy proceeds, FUNDC1/calnexin association attenuates and the exposed cytosolic loop of FUNDC1 interacts with DRP1 instead. DRP1 is thereby recruited to the MAM, and mitochondrial fission then occurs. Knockdown of FUNDC1, DRP1, or calnexin prevents fission and mitophagy under hypoxic conditions. Thus, FUNDC1 integrates mitochondrial fission and mitophagy at the interface of the MAM by working in concert with DRP1 and calnexin under hypoxic conditions in mammalian cells.
Synopsis
In response to hypoxia, mitophagy receptor FUNDC1 associates with ER‐resident protein calnexin and thereby accumulates at the ER–mitochondrial contact site; this allows for DRP‐1 recruitment and thus mitochondrial fission.
FUNDC1 accumulates at the ER–mitochondrial contact site (MAM) by association with calnexin in response to hypoxia.
FUNDC1 mediates mitochondrial fission in response to hypoxia.
FUNDC1 binds to DRP1 for mitochondrial fission during hypoxia.
FUNDC1 is the molecular link that integrates mitochondrial fission and mitophagy at the interface of the MAM.
Graphical Abstract
In response to hypoxia, mitophagy receptor FUNDC1 associates with ER‐resident protein calnexin and thereby accumulates at the ER–mitochondrial contact site; this allows for DRP‐1 recruitment and thus mitochondrial fission.</description><subject>autophagy</subject><subject>Calnexin - metabolism</subject><subject>Cells, Cultured</subject><subject>Cellular biology</subject><subject>Dynamins</subject><subject>EMBO07</subject><subject>EMBO20</subject><subject>EMBO21</subject><subject>Endoplasmic Reticulum - metabolism</subject><subject>ER-mitochondrial contact site</subject><subject>GTP Phosphohydrolases - metabolism</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>MAM</subject><subject>Membrane Proteins - metabolism</subject><subject>Microtubule-Associated Proteins - metabolism</subject><subject>Mitochondria</subject><subject>Mitochondrial Dynamics</subject><subject>mitochondrial fission</subject><subject>Mitochondrial Proteins - metabolism</subject><subject>Mitophagy</subject><subject>Protein Binding</subject><subject>Proteins</subject><issn>0261-4189</issn><issn>1460-2075</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkc1uEzEUhS0EoqGwZodGYsNmin9nHBZIbUhTqlKkigp2lsf2JA4zdrA9bfM2PAtPhmnKqEWsLOt859x7dQB4ieABYpjht6Zv1gcYIjYlCOJHYIJoBUsMa_YYTCCuUEkRn-6BZzGuIYSM1-gp2MM1otlBJqA9vjz_MENFMMuhk8nEorfJq5V3OljZFXrrZG9VLGQq0soU84vyIaC8S1KlItpkisFpE4rVduNvrPr1M2vaJutdfA6etLKL5sXduw8uj-dfZifl2efFx9nhWWlZRXFJVNNOFWSEaNqwttXEtLWmitNKIkgoVIplkTWy0Y1Rhplpg3TFEOeK1YqSffB-l7sZmt5oZVwKshObYHsZtsJLKx4qzq7E0l8JyvN8DnPAm7uA4H8MJibR26hM10ln_BAF4hBRQjkhGX39D7r2Q3D5vFuKcIJrlqlX9zcaV_lbQQbe7YBr25ntqCMobhsWfxoWY8Ni_unodPxlM9yZY_a5pQn3dvh_QLaUO4uNydyM82T4Lqqa1Ex8PV-Ii4rg06PFifhGfgMyvLuZ</recordid><startdate>20160701</startdate><enddate>20160701</enddate><creator>Wu, Wenxian</creator><creator>Lin, Chunxia</creator><creator>Wu, Keng</creator><creator>Jiang, Lei</creator><creator>Wang, Xiaojing</creator><creator>Li, Wen</creator><creator>Zhuang, Haixia</creator><creator>Zhang, Xingliang</creator><creator>Chen, Hao</creator><creator>Li, Shupeng</creator><creator>Yang, Yue</creator><creator>Lu, Yue</creator><creator>Wang, Jingjing</creator><creator>Zhu, Runzhi</creator><creator>Zhang, Liangqing</creator><creator>Sui, Senfang</creator><creator>Tan, Ning</creator><creator>Zhao, Bin</creator><creator>Zhang, Jingjing</creator><creator>Li, Longxuan</creator><creator>Feng, Du</creator><general>Blackwell Publishing Ltd</general><general>Nature Publishing Group UK</general><general>John Wiley and Sons Inc</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-2489-4702</orcidid></search><sort><creationdate>20160701</creationdate><title>FUNDC1 regulates mitochondrial dynamics at the ER-mitochondrial contact site under hypoxic conditions</title><author>Wu, Wenxian ; Lin, Chunxia ; Wu, Keng ; Jiang, Lei ; Wang, Xiaojing ; Li, Wen ; Zhuang, Haixia ; Zhang, Xingliang ; Chen, Hao ; Li, Shupeng ; Yang, Yue ; Lu, Yue ; Wang, Jingjing ; Zhu, Runzhi ; Zhang, Liangqing ; Sui, Senfang ; Tan, Ning ; Zhao, Bin ; Zhang, Jingjing ; Li, Longxuan ; Feng, Du</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-i5642-3cbf9c0533d4b5ffd3ef7d4c846a10340cc55335babdbece5e9b1d65188c57c43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>autophagy</topic><topic>Calnexin - metabolism</topic><topic>Cells, Cultured</topic><topic>Cellular biology</topic><topic>Dynamins</topic><topic>EMBO07</topic><topic>EMBO20</topic><topic>EMBO21</topic><topic>Endoplasmic Reticulum - metabolism</topic><topic>ER-mitochondrial contact site</topic><topic>GTP Phosphohydrolases - metabolism</topic><topic>Humans</topic><topic>Hypoxia</topic><topic>MAM</topic><topic>Membrane Proteins - metabolism</topic><topic>Microtubule-Associated Proteins - metabolism</topic><topic>Mitochondria</topic><topic>Mitochondrial Dynamics</topic><topic>mitochondrial fission</topic><topic>Mitochondrial Proteins - metabolism</topic><topic>Mitophagy</topic><topic>Protein Binding</topic><topic>Proteins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Wenxian</creatorcontrib><creatorcontrib>Lin, Chunxia</creatorcontrib><creatorcontrib>Wu, Keng</creatorcontrib><creatorcontrib>Jiang, Lei</creatorcontrib><creatorcontrib>Wang, Xiaojing</creatorcontrib><creatorcontrib>Li, Wen</creatorcontrib><creatorcontrib>Zhuang, Haixia</creatorcontrib><creatorcontrib>Zhang, Xingliang</creatorcontrib><creatorcontrib>Chen, Hao</creatorcontrib><creatorcontrib>Li, Shupeng</creatorcontrib><creatorcontrib>Yang, Yue</creatorcontrib><creatorcontrib>Lu, Yue</creatorcontrib><creatorcontrib>Wang, Jingjing</creatorcontrib><creatorcontrib>Zhu, Runzhi</creatorcontrib><creatorcontrib>Zhang, Liangqing</creatorcontrib><creatorcontrib>Sui, Senfang</creatorcontrib><creatorcontrib>Tan, Ning</creatorcontrib><creatorcontrib>Zhao, Bin</creatorcontrib><creatorcontrib>Zhang, Jingjing</creatorcontrib><creatorcontrib>Li, Longxuan</creatorcontrib><creatorcontrib>Feng, Du</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The EMBO journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Wu, Wenxian</au><au>Lin, Chunxia</au><au>Wu, Keng</au><au>Jiang, Lei</au><au>Wang, Xiaojing</au><au>Li, Wen</au><au>Zhuang, Haixia</au><au>Zhang, Xingliang</au><au>Chen, Hao</au><au>Li, Shupeng</au><au>Yang, Yue</au><au>Lu, Yue</au><au>Wang, Jingjing</au><au>Zhu, Runzhi</au><au>Zhang, Liangqing</au><au>Sui, Senfang</au><au>Tan, Ning</au><au>Zhao, Bin</au><au>Zhang, Jingjing</au><au>Li, Longxuan</au><au>Feng, Du</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>FUNDC1 regulates mitochondrial dynamics at the ER-mitochondrial contact site under hypoxic conditions</atitle><jtitle>The EMBO journal</jtitle><stitle>EMBO J</stitle><addtitle>EMBO J</addtitle><date>2016-07-01</date><risdate>2016</risdate><volume>35</volume><issue>13</issue><spage>1368</spage><epage>1384</epage><pages>1368-1384</pages><issn>0261-4189</issn><eissn>1460-2075</eissn><coden>EMJODG</coden><abstract>In hypoxic cells, dysfunctional mitochondria are selectively removed by a specialized autophagic process called mitophagy. The ER–mitochondrial contact site (MAM) is essential for fission of mitochondria prior to engulfment, and the outer mitochondrial membrane protein FUNDC1 interacts with LC3 to recruit autophagosomes, but the mechanisms integrating these processes are poorly understood. Here, we describe a new pathway mediating mitochondrial fission and subsequent mitophagy under hypoxic conditions. FUNDC1 accumulates at the MAM by associating with the ER membrane protein calnexin. As mitophagy proceeds, FUNDC1/calnexin association attenuates and the exposed cytosolic loop of FUNDC1 interacts with DRP1 instead. DRP1 is thereby recruited to the MAM, and mitochondrial fission then occurs. Knockdown of FUNDC1, DRP1, or calnexin prevents fission and mitophagy under hypoxic conditions. Thus, FUNDC1 integrates mitochondrial fission and mitophagy at the interface of the MAM by working in concert with DRP1 and calnexin under hypoxic conditions in mammalian cells.
Synopsis
In response to hypoxia, mitophagy receptor FUNDC1 associates with ER‐resident protein calnexin and thereby accumulates at the ER–mitochondrial contact site; this allows for DRP‐1 recruitment and thus mitochondrial fission.
FUNDC1 accumulates at the ER–mitochondrial contact site (MAM) by association with calnexin in response to hypoxia.
FUNDC1 mediates mitochondrial fission in response to hypoxia.
FUNDC1 binds to DRP1 for mitochondrial fission during hypoxia.
FUNDC1 is the molecular link that integrates mitochondrial fission and mitophagy at the interface of the MAM.
Graphical Abstract
In response to hypoxia, mitophagy receptor FUNDC1 associates with ER‐resident protein calnexin and thereby accumulates at the ER–mitochondrial contact site; this allows for DRP‐1 recruitment and thus mitochondrial fission.</abstract><cop>London</cop><pub>Blackwell Publishing Ltd</pub><pmid>27145933</pmid><doi>10.15252/embj.201593102</doi><tpages>17</tpages><orcidid>https://orcid.org/0000-0002-2489-4702</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext_linktorsrc |
identifier | ISSN: 0261-4189 |
ispartof | The EMBO journal, 2016-07, Vol.35 (13), p.1368-1384 |
issn | 0261-4189 1460-2075 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4864280 |
source | Springer Nature OA/Free Journals |
subjects | autophagy Calnexin - metabolism Cells, Cultured Cellular biology Dynamins EMBO07 EMBO20 EMBO21 Endoplasmic Reticulum - metabolism ER-mitochondrial contact site GTP Phosphohydrolases - metabolism Humans Hypoxia MAM Membrane Proteins - metabolism Microtubule-Associated Proteins - metabolism Mitochondria Mitochondrial Dynamics mitochondrial fission Mitochondrial Proteins - metabolism Mitophagy Protein Binding Proteins |
title | FUNDC1 regulates mitochondrial dynamics at the ER-mitochondrial contact site under hypoxic conditions |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-05T14%3A16%3A16IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_C6C&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=FUNDC1%20regulates%20mitochondrial%20dynamics%20at%20the%20ER-mitochondrial%20contact%20site%20under%20hypoxic%C2%A0conditions&rft.jtitle=The%20EMBO%20journal&rft.au=Wu,%20Wenxian&rft.date=2016-07-01&rft.volume=35&rft.issue=13&rft.spage=1368&rft.epage=1384&rft.pages=1368-1384&rft.issn=0261-4189&rft.eissn=1460-2075&rft.coden=EMJODG&rft_id=info:doi/10.15252/embj.201593102&rft_dat=%3Cproquest_C6C%3E4106970461%3C/proquest_C6C%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1801383275&rft_id=info:pmid/27145933&rfr_iscdi=true |