SUMO-Modified FADD Recruits Cytosolic Drp1 and Caspase-10 to Mitochondria for Regulated Necrosis
Fas-associated protein with death domain (FADD) plays a key role in extrinsic apoptosis. Here, we show that FADD is SUMOylated as an essential step during intrinsic necrosis. FADD was modified at multiple lysine residues (K120/125/149) by small ubiquitin-related modifier 2 (SUMO2) during necrosis ca...
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| Veröffentlicht in: | Molecular and cellular biology 2017-01, Vol.37 (2) |
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| creator | Choi, Seon-Guk Kim, Hyunjoo Jeong, Eun Il Lee, Ho-June Park, Sungwoo Lee, Song-Yi Lee, Hyeon-Jeong Lee, Seong Won Chung, Chin Ha Jung, Yong-Keun |
| description | Fas-associated protein with death domain (FADD) plays a key role in extrinsic apoptosis. Here, we show that FADD is SUMOylated as an essential step during intrinsic necrosis. FADD was modified at multiple lysine residues (K120/125/149) by small ubiquitin-related modifier 2 (SUMO2) during necrosis caused by calcium ionophore A23187 and by ischemic damage. SUMOylated FADD bound to dynamin-related protein 1 (Drp1) in cells both in vitro and in ischemic tissue damage cores, thus promoting Drp1 recruitment by mitochondrial fission factor (Mff) to accomplish mitochondrial fragmentation. Mitochondrial-fragmentation-associated necrosis was blocked by FADD or Drp1 deficiency and SUMO-defective FADD expression. Interestingly, caspase-10, but not caspase-8, formed a ternary protein complex with SUMO-FADD/Drp1 on the mitochondria upon exposure to A23187 and potentiated Drp1 oligomerization for necrosis. Moreover, the caspase-10 L285F and A414V mutants, found in autoimmune lymphoproliferative syndrome and non-Hodgkin lymphoma, respectively, regulated this necrosis. Our study reveals an essential role of SUMOylated FADD in Drp1- and caspase-10-dependent necrosis, providing insights into the mechanism of regulated necrosis by calcium overload and ischemic injury. |
| doi_str_mv | 10.1128/MCB.00254-16 |
| format | Article |
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Here, we show that FADD is SUMOylated as an essential step during intrinsic necrosis. FADD was modified at multiple lysine residues (K120/125/149) by small ubiquitin-related modifier 2 (SUMO2) during necrosis caused by calcium ionophore A23187 and by ischemic damage. SUMOylated FADD bound to dynamin-related protein 1 (Drp1) in cells both in vitro and in ischemic tissue damage cores, thus promoting Drp1 recruitment by mitochondrial fission factor (Mff) to accomplish mitochondrial fragmentation. Mitochondrial-fragmentation-associated necrosis was blocked by FADD or Drp1 deficiency and SUMO-defective FADD expression. Interestingly, caspase-10, but not caspase-8, formed a ternary protein complex with SUMO-FADD/Drp1 on the mitochondria upon exposure to A23187 and potentiated Drp1 oligomerization for necrosis. Moreover, the caspase-10 L285F and A414V mutants, found in autoimmune lymphoproliferative syndrome and non-Hodgkin lymphoma, respectively, regulated this necrosis. Our study reveals an essential role of SUMOylated FADD in Drp1- and caspase-10-dependent necrosis, providing insights into the mechanism of regulated necrosis by calcium overload and ischemic injury.</description><identifier>ISSN: 1098-5549</identifier><identifier>ISSN: 0270-7306</identifier><identifier>EISSN: 1098-5549</identifier><identifier>DOI: 10.1128/MCB.00254-16</identifier><identifier>PMID: 27799292</identifier><language>eng</language><publisher>United States: Taylor & Francis</publisher><subject>Animals ; Caspase 10 - metabolism ; caspase-10 ; Cell Hypoxia ; Cytosol - metabolism ; DRP1 ; Dynamins - metabolism ; FADD ; Fas-Associated Death Domain Protein - metabolism ; HEK293 Cells ; HeLa Cells ; Humans ; Lysine - metabolism ; Mice, Inbred C57BL ; Mitochondria - metabolism ; Multiprotein Complexes - metabolism ; Mutant Proteins - metabolism ; Necrosis ; Protein Binding ; Protein Multimerization ; Protein Transport ; RNA, Small Interfering - metabolism ; Small Ubiquitin-Related Modifier Proteins - metabolism ; SUMO-1 Protein - metabolism ; SUMOylation</subject><ispartof>Molecular and cellular biology, 2017-01, Vol.37 (2)</ispartof><rights>Copyright © 2017 American Society for Microbiology 2017</rights><rights>Copyright © 2017 American Society for Microbiology.</rights><rights>Copyright © 2017 American Society for Microbiology. 2017 American Society for Microbiology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c432t-ff7fea1fce0698661e1a44e18428107af9a6f7bc95bbe2c23430f28ae15934dc3</citedby><cites>FETCH-LOGICAL-c432t-ff7fea1fce0698661e1a44e18428107af9a6f7bc95bbe2c23430f28ae15934dc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5214857/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5214857/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,315,728,781,785,886,27929,27930,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27799292$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Choi, Seon-Guk</creatorcontrib><creatorcontrib>Kim, Hyunjoo</creatorcontrib><creatorcontrib>Jeong, Eun Il</creatorcontrib><creatorcontrib>Lee, Ho-June</creatorcontrib><creatorcontrib>Park, Sungwoo</creatorcontrib><creatorcontrib>Lee, Song-Yi</creatorcontrib><creatorcontrib>Lee, Hyeon-Jeong</creatorcontrib><creatorcontrib>Lee, Seong Won</creatorcontrib><creatorcontrib>Chung, Chin Ha</creatorcontrib><creatorcontrib>Jung, Yong-Keun</creatorcontrib><title>SUMO-Modified FADD Recruits Cytosolic Drp1 and Caspase-10 to Mitochondria for Regulated Necrosis</title><title>Molecular and cellular biology</title><addtitle>Mol Cell Biol</addtitle><description>Fas-associated protein with death domain (FADD) plays a key role in extrinsic apoptosis. Here, we show that FADD is SUMOylated as an essential step during intrinsic necrosis. FADD was modified at multiple lysine residues (K120/125/149) by small ubiquitin-related modifier 2 (SUMO2) during necrosis caused by calcium ionophore A23187 and by ischemic damage. SUMOylated FADD bound to dynamin-related protein 1 (Drp1) in cells both in vitro and in ischemic tissue damage cores, thus promoting Drp1 recruitment by mitochondrial fission factor (Mff) to accomplish mitochondrial fragmentation. Mitochondrial-fragmentation-associated necrosis was blocked by FADD or Drp1 deficiency and SUMO-defective FADD expression. Interestingly, caspase-10, but not caspase-8, formed a ternary protein complex with SUMO-FADD/Drp1 on the mitochondria upon exposure to A23187 and potentiated Drp1 oligomerization for necrosis. Moreover, the caspase-10 L285F and A414V mutants, found in autoimmune lymphoproliferative syndrome and non-Hodgkin lymphoma, respectively, regulated this necrosis. Our study reveals an essential role of SUMOylated FADD in Drp1- and caspase-10-dependent necrosis, providing insights into the mechanism of regulated necrosis by calcium overload and ischemic injury.</description><subject>Animals</subject><subject>Caspase 10 - metabolism</subject><subject>caspase-10</subject><subject>Cell Hypoxia</subject><subject>Cytosol - metabolism</subject><subject>DRP1</subject><subject>Dynamins - metabolism</subject><subject>FADD</subject><subject>Fas-Associated Death Domain Protein - metabolism</subject><subject>HEK293 Cells</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Lysine - metabolism</subject><subject>Mice, Inbred C57BL</subject><subject>Mitochondria - metabolism</subject><subject>Multiprotein Complexes - metabolism</subject><subject>Mutant Proteins - metabolism</subject><subject>Necrosis</subject><subject>Protein Binding</subject><subject>Protein Multimerization</subject><subject>Protein Transport</subject><subject>RNA, Small Interfering - metabolism</subject><subject>Small Ubiquitin-Related Modifier Proteins - metabolism</subject><subject>SUMO-1 Protein - metabolism</subject><subject>SUMOylation</subject><issn>1098-5549</issn><issn>0270-7306</issn><issn>1098-5549</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkc1PHCEYh0nTpn60t54bjj10LC_DfHAxsbN-Ja4mbT3TdxlQzOywBaZm_3vRVaOJJ0h4ePi9_Aj5AmwPgLc_5t3PPcZ4JQqo35FtYLItqkrI9y_2W2QnxhvGWC1Z-ZFs8aaRkku-Tf7-vpxfFHPfO-tMT48OZjP6y-gwuRRpt04--sFpOgsroDj2tMO4wmgKYDR5OnfJ62s_9sEhtT7kq1fTgCmbzrPERxc_kQ8Wh2g-P6675PLo8E93UpxdHJ92B2eFFiVPhbWNNQhWm5yxrWswgEIYaAVvgTVoJda2WWhZLRaGa16KklneooFKlqLX5S7Z33hX02Jpem3GFHBQq-CWGNbKo1OvT0Z3ra78f1VxEG3VZMG3R0Hw_yYTk1q6qM0w4Gj8FBW0ZcVYDisy-n2D3o8Yg7HPzwBT96WoXIp6KEVBnfGvL6M9w08tZKDZAG7Mn7jEWx-GXiVcDz7YgKN2UZVvqu8A4QCaFw</recordid><startdate>20170101</startdate><enddate>20170101</enddate><creator>Choi, Seon-Guk</creator><creator>Kim, Hyunjoo</creator><creator>Jeong, Eun Il</creator><creator>Lee, Ho-June</creator><creator>Park, Sungwoo</creator><creator>Lee, Song-Yi</creator><creator>Lee, Hyeon-Jeong</creator><creator>Lee, Seong Won</creator><creator>Chung, Chin Ha</creator><creator>Jung, Yong-Keun</creator><general>Taylor & Francis</general><general>American Society for Microbiology</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20170101</creationdate><title>SUMO-Modified FADD Recruits Cytosolic Drp1 and Caspase-10 to Mitochondria for Regulated Necrosis</title><author>Choi, Seon-Guk ; Kim, Hyunjoo ; Jeong, Eun Il ; Lee, Ho-June ; Park, Sungwoo ; Lee, Song-Yi ; Lee, Hyeon-Jeong ; Lee, Seong Won ; Chung, Chin Ha ; Jung, Yong-Keun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c432t-ff7fea1fce0698661e1a44e18428107af9a6f7bc95bbe2c23430f28ae15934dc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Caspase 10 - metabolism</topic><topic>caspase-10</topic><topic>Cell Hypoxia</topic><topic>Cytosol - metabolism</topic><topic>DRP1</topic><topic>Dynamins - metabolism</topic><topic>FADD</topic><topic>Fas-Associated Death Domain Protein - metabolism</topic><topic>HEK293 Cells</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Lysine - metabolism</topic><topic>Mice, Inbred C57BL</topic><topic>Mitochondria - metabolism</topic><topic>Multiprotein Complexes - metabolism</topic><topic>Mutant Proteins - metabolism</topic><topic>Necrosis</topic><topic>Protein Binding</topic><topic>Protein Multimerization</topic><topic>Protein Transport</topic><topic>RNA, Small Interfering - metabolism</topic><topic>Small Ubiquitin-Related Modifier Proteins - metabolism</topic><topic>SUMO-1 Protein - metabolism</topic><topic>SUMOylation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Choi, Seon-Guk</creatorcontrib><creatorcontrib>Kim, Hyunjoo</creatorcontrib><creatorcontrib>Jeong, Eun Il</creatorcontrib><creatorcontrib>Lee, Ho-June</creatorcontrib><creatorcontrib>Park, Sungwoo</creatorcontrib><creatorcontrib>Lee, Song-Yi</creatorcontrib><creatorcontrib>Lee, Hyeon-Jeong</creatorcontrib><creatorcontrib>Lee, Seong Won</creatorcontrib><creatorcontrib>Chung, Chin Ha</creatorcontrib><creatorcontrib>Jung, Yong-Keun</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular and cellular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Choi, Seon-Guk</au><au>Kim, Hyunjoo</au><au>Jeong, Eun Il</au><au>Lee, Ho-June</au><au>Park, Sungwoo</au><au>Lee, Song-Yi</au><au>Lee, Hyeon-Jeong</au><au>Lee, Seong Won</au><au>Chung, Chin Ha</au><au>Jung, Yong-Keun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>SUMO-Modified FADD Recruits Cytosolic Drp1 and Caspase-10 to Mitochondria for Regulated Necrosis</atitle><jtitle>Molecular and cellular biology</jtitle><addtitle>Mol Cell Biol</addtitle><date>2017-01-01</date><risdate>2017</risdate><volume>37</volume><issue>2</issue><issn>1098-5549</issn><issn>0270-7306</issn><eissn>1098-5549</eissn><abstract>Fas-associated protein with death domain (FADD) plays a key role in extrinsic apoptosis. Here, we show that FADD is SUMOylated as an essential step during intrinsic necrosis. FADD was modified at multiple lysine residues (K120/125/149) by small ubiquitin-related modifier 2 (SUMO2) during necrosis caused by calcium ionophore A23187 and by ischemic damage. SUMOylated FADD bound to dynamin-related protein 1 (Drp1) in cells both in vitro and in ischemic tissue damage cores, thus promoting Drp1 recruitment by mitochondrial fission factor (Mff) to accomplish mitochondrial fragmentation. Mitochondrial-fragmentation-associated necrosis was blocked by FADD or Drp1 deficiency and SUMO-defective FADD expression. Interestingly, caspase-10, but not caspase-8, formed a ternary protein complex with SUMO-FADD/Drp1 on the mitochondria upon exposure to A23187 and potentiated Drp1 oligomerization for necrosis. Moreover, the caspase-10 L285F and A414V mutants, found in autoimmune lymphoproliferative syndrome and non-Hodgkin lymphoma, respectively, regulated this necrosis. Our study reveals an essential role of SUMOylated FADD in Drp1- and caspase-10-dependent necrosis, providing insights into the mechanism of regulated necrosis by calcium overload and ischemic injury.</abstract><cop>United States</cop><pub>Taylor & Francis</pub><pmid>27799292</pmid><doi>10.1128/MCB.00254-16</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Caspase 10 - metabolism caspase-10 Cell Hypoxia Cytosol - metabolism DRP1 Dynamins - metabolism FADD Fas-Associated Death Domain Protein - metabolism HEK293 Cells HeLa Cells Humans Lysine - metabolism Mice, Inbred C57BL Mitochondria - metabolism Multiprotein Complexes - metabolism Mutant Proteins - metabolism Necrosis Protein Binding Protein Multimerization Protein Transport RNA, Small Interfering - metabolism Small Ubiquitin-Related Modifier Proteins - metabolism SUMO-1 Protein - metabolism SUMOylation |
| title | SUMO-Modified FADD Recruits Cytosolic Drp1 and Caspase-10 to Mitochondria for Regulated Necrosis |
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