dynamin-related GTPase Drp1 is required for embryonic and brain development in mice
The dynamin-related guanosine triphosphatase Drp1 mediates the division of mitochondria and peroxisomes. To understand the in vivo function of Drp1, complete and tissue-specific mouse knockouts of Drp1 were generated. Drp1-null mice die by embryonic day 11.5. This embryonic lethality is not likely c...
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Veröffentlicht in: | The Journal of cell biology 2009-09, Vol.186 (6), p.805-816 |
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container_title | The Journal of cell biology |
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creator | Wakabayashi, Junko Zhang, Zhongyan Wakabayashi, Nobunao Tamura, Yasushi Fukaya, Masahiro Kensler, Thomas W Iijima, Miho Sesaki, Hiromi |
description | The dynamin-related guanosine triphosphatase Drp1 mediates the division of mitochondria and peroxisomes. To understand the in vivo function of Drp1, complete and tissue-specific mouse knockouts of Drp1 were generated. Drp1-null mice die by embryonic day 11.5. This embryonic lethality is not likely caused by gross energy deprivation, as Drp1-null cells showed normal intracellular adenosine triphosphate levels. In support of the role of Drp1 in organelle division, mitochondria formed extensive networks, and peroxisomes were elongated in Drp1-null embryonic fibroblasts. Brain-specific Drp1 ablation caused developmental defects of the cerebellum in which Purkinje cells contained few giant mitochondria instead of the many short tubular mitochondria observed in control cells. In addition, Drp1-null embryos failed to undergo developmentally regulated apoptosis during neural tube formation in vivo. However, Drp1-null embryonic fibroblasts have normal responses to apoptotic stimuli in vitro, suggesting that the apoptotic function of Drp1 depends on physiological cues. These findings clearly demonstrate the physiological importance of Drp1-mediated organelle division in mice. |
doi_str_mv | 10.1083/jcb.200903065 |
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To understand the in vivo function of Drp1, complete and tissue-specific mouse knockouts of Drp1 were generated. Drp1-null mice die by embryonic day 11.5. This embryonic lethality is not likely caused by gross energy deprivation, as Drp1-null cells showed normal intracellular adenosine triphosphate levels. In support of the role of Drp1 in organelle division, mitochondria formed extensive networks, and peroxisomes were elongated in Drp1-null embryonic fibroblasts. Brain-specific Drp1 ablation caused developmental defects of the cerebellum in which Purkinje cells contained few giant mitochondria instead of the many short tubular mitochondria observed in control cells. In addition, Drp1-null embryos failed to undergo developmentally regulated apoptosis during neural tube formation in vivo. However, Drp1-null embryonic fibroblasts have normal responses to apoptotic stimuli in vitro, suggesting that the apoptotic function of Drp1 depends on physiological cues. These findings clearly demonstrate the physiological importance of Drp1-mediated organelle division in mice.</description><identifier>ISSN: 0021-9525</identifier><identifier>EISSN: 1540-8140</identifier><identifier>DOI: 10.1083/jcb.200903065</identifier><identifier>PMID: 19752021</identifier><identifier>CODEN: JCLBA3</identifier><language>eng</language><publisher>United States: The Rockefeller University Press</publisher><subject>Adenosine triphosphatase ; Adenosine Triphosphate - metabolism ; Animals ; Antibodies ; Apoptosis ; Brain ; Cells, Cultured ; Cellular biology ; Cerebellum ; Cerebellum - embryology ; Cerebellum - enzymology ; Cerebellum - ultrastructure ; Cytochromes ; Dynamins ; Embryology ; Embryos ; Fibroblasts - enzymology ; Fibroblasts - ultrastructure ; Gestational Age ; Giant cells ; Giant Cells - enzymology ; Giant Cells - ultrastructure ; GTP Phosphohydrolases - deficiency ; GTP Phosphohydrolases - genetics ; GTP Phosphohydrolases - metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microtubule-Associated Proteins - deficiency ; Microtubule-Associated Proteins - genetics ; Microtubule-Associated Proteins - metabolism ; Mitochondria ; Mitochondria - enzymology ; Mitochondria - ultrastructure ; Mitochondrial Size ; Myocytes, Cardiac - enzymology ; Myocytes, Cardiac - ultrastructure ; Neurons ; Organelle Shape ; Organogenesis ; Peroxisomes ; Peroxisomes - enzymology ; Peroxisomes - ultrastructure ; Purkinje Cells - diagnostic imaging ; Purkinje Cells - enzymology ; Rodents ; Trophoblasts - enzymology ; Trophoblasts - ultrastructure ; Ultrasonography</subject><ispartof>The Journal of cell biology, 2009-09, Vol.186 (6), p.805-816</ispartof><rights>Copyright Rockefeller University Press Sep 21, 2009</rights><rights>2009 Wakabayashi et al. 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c524t-66b2543bcc6cc2ee76d7595a5099780dd2d44d747b2e46206978e530f94811743</citedby><cites>FETCH-LOGICAL-c524t-66b2543bcc6cc2ee76d7595a5099780dd2d44d747b2e46206978e530f94811743</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19752021$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wakabayashi, Junko</creatorcontrib><creatorcontrib>Zhang, Zhongyan</creatorcontrib><creatorcontrib>Wakabayashi, Nobunao</creatorcontrib><creatorcontrib>Tamura, Yasushi</creatorcontrib><creatorcontrib>Fukaya, Masahiro</creatorcontrib><creatorcontrib>Kensler, Thomas W</creatorcontrib><creatorcontrib>Iijima, Miho</creatorcontrib><creatorcontrib>Sesaki, Hiromi</creatorcontrib><title>dynamin-related GTPase Drp1 is required for embryonic and brain development in mice</title><title>The Journal of cell biology</title><addtitle>J Cell Biol</addtitle><description>The dynamin-related guanosine triphosphatase Drp1 mediates the division of mitochondria and peroxisomes. To understand the in vivo function of Drp1, complete and tissue-specific mouse knockouts of Drp1 were generated. Drp1-null mice die by embryonic day 11.5. This embryonic lethality is not likely caused by gross energy deprivation, as Drp1-null cells showed normal intracellular adenosine triphosphate levels. In support of the role of Drp1 in organelle division, mitochondria formed extensive networks, and peroxisomes were elongated in Drp1-null embryonic fibroblasts. Brain-specific Drp1 ablation caused developmental defects of the cerebellum in which Purkinje cells contained few giant mitochondria instead of the many short tubular mitochondria observed in control cells. In addition, Drp1-null embryos failed to undergo developmentally regulated apoptosis during neural tube formation in vivo. However, Drp1-null embryonic fibroblasts have normal responses to apoptotic stimuli in vitro, suggesting that the apoptotic function of Drp1 depends on physiological cues. These findings clearly demonstrate the physiological importance of Drp1-mediated organelle division in mice.</description><subject>Adenosine triphosphatase</subject><subject>Adenosine Triphosphate - metabolism</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Apoptosis</subject><subject>Brain</subject><subject>Cells, Cultured</subject><subject>Cellular biology</subject><subject>Cerebellum</subject><subject>Cerebellum - embryology</subject><subject>Cerebellum - enzymology</subject><subject>Cerebellum - ultrastructure</subject><subject>Cytochromes</subject><subject>Dynamins</subject><subject>Embryology</subject><subject>Embryos</subject><subject>Fibroblasts - enzymology</subject><subject>Fibroblasts - ultrastructure</subject><subject>Gestational Age</subject><subject>Giant cells</subject><subject>Giant Cells - enzymology</subject><subject>Giant Cells - ultrastructure</subject><subject>GTP Phosphohydrolases - deficiency</subject><subject>GTP Phosphohydrolases - genetics</subject><subject>GTP Phosphohydrolases - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Microtubule-Associated Proteins - deficiency</subject><subject>Microtubule-Associated Proteins - genetics</subject><subject>Microtubule-Associated Proteins - metabolism</subject><subject>Mitochondria</subject><subject>Mitochondria - enzymology</subject><subject>Mitochondria - ultrastructure</subject><subject>Mitochondrial Size</subject><subject>Myocytes, Cardiac - enzymology</subject><subject>Myocytes, Cardiac - ultrastructure</subject><subject>Neurons</subject><subject>Organelle Shape</subject><subject>Organogenesis</subject><subject>Peroxisomes</subject><subject>Peroxisomes - enzymology</subject><subject>Peroxisomes - ultrastructure</subject><subject>Purkinje Cells - diagnostic imaging</subject><subject>Purkinje Cells - enzymology</subject><subject>Rodents</subject><subject>Trophoblasts - enzymology</subject><subject>Trophoblasts - ultrastructure</subject><subject>Ultrasonography</subject><issn>0021-9525</issn><issn>1540-8140</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc2L1EAQxRtR3HH06FENHrxlrf5OLoKsugoLCrt7bjrdlbWHJD3bnSzMf29LhvHjVFS9H49XPEJeUjin0PD3O9edM4AWOCj5iGyoFFA3VMBjsgFgtG4lk2fkWc47ABBa8KfkjLZasiJuyLU_THYMU51wsDP66vLmh81YfUp7WoVcJbxfQir3PqYKxy4d4hRcZSdfdcmGqfL4gEPcjzjNVVnH4PA5edLbIeOL49yS2y-fby6-1lffL79dfLyqnWRirpXqmBS8c045xxC18lq20kpoW92A98wL4bXQHUOhGKhyRcmhb0VDaXlkSz6svvulG9G7EiHZwexTGG06mGiD-VeZwk9zFx8M05JTqYrBu6NBivcL5tmMITscBjthXLJRWumWM1bAt_-Bu7ikqTxnGNWUClUct6ReIZdizgn7UxIK5ndXpnRlTl0V_vXf8f_Qx3IK8GoFdnmO6aQL4I1YDd6sem-jsXcpZHN7zYByoKoRVDP-C4BKoUA</recordid><startdate>20090921</startdate><enddate>20090921</enddate><creator>Wakabayashi, Junko</creator><creator>Zhang, Zhongyan</creator><creator>Wakabayashi, Nobunao</creator><creator>Tamura, Yasushi</creator><creator>Fukaya, Masahiro</creator><creator>Kensler, Thomas W</creator><creator>Iijima, Miho</creator><creator>Sesaki, Hiromi</creator><general>The Rockefeller University Press</general><general>Rockefeller University Press</general><scope>FBQ</scope><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>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20090921</creationdate><title>dynamin-related GTPase Drp1 is required for embryonic and brain development in mice</title><author>Wakabayashi, Junko ; Zhang, Zhongyan ; Wakabayashi, Nobunao ; Tamura, Yasushi ; Fukaya, Masahiro ; Kensler, Thomas W ; Iijima, Miho ; Sesaki, Hiromi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c524t-66b2543bcc6cc2ee76d7595a5099780dd2d44d747b2e46206978e530f94811743</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adenosine triphosphatase</topic><topic>Adenosine Triphosphate - metabolism</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Apoptosis</topic><topic>Brain</topic><topic>Cells, Cultured</topic><topic>Cellular biology</topic><topic>Cerebellum</topic><topic>Cerebellum - embryology</topic><topic>Cerebellum - enzymology</topic><topic>Cerebellum - ultrastructure</topic><topic>Cytochromes</topic><topic>Dynamins</topic><topic>Embryology</topic><topic>Embryos</topic><topic>Fibroblasts - enzymology</topic><topic>Fibroblasts - ultrastructure</topic><topic>Gestational Age</topic><topic>Giant cells</topic><topic>Giant Cells - enzymology</topic><topic>Giant Cells - ultrastructure</topic><topic>GTP Phosphohydrolases - deficiency</topic><topic>GTP Phosphohydrolases - genetics</topic><topic>GTP Phosphohydrolases - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Microtubule-Associated Proteins - deficiency</topic><topic>Microtubule-Associated Proteins - genetics</topic><topic>Microtubule-Associated Proteins - metabolism</topic><topic>Mitochondria</topic><topic>Mitochondria - enzymology</topic><topic>Mitochondria - ultrastructure</topic><topic>Mitochondrial Size</topic><topic>Myocytes, Cardiac - enzymology</topic><topic>Myocytes, Cardiac - ultrastructure</topic><topic>Neurons</topic><topic>Organelle Shape</topic><topic>Organogenesis</topic><topic>Peroxisomes</topic><topic>Peroxisomes - enzymology</topic><topic>Peroxisomes - ultrastructure</topic><topic>Purkinje Cells - diagnostic imaging</topic><topic>Purkinje Cells - enzymology</topic><topic>Rodents</topic><topic>Trophoblasts - enzymology</topic><topic>Trophoblasts - ultrastructure</topic><topic>Ultrasonography</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wakabayashi, Junko</creatorcontrib><creatorcontrib>Zhang, Zhongyan</creatorcontrib><creatorcontrib>Wakabayashi, Nobunao</creatorcontrib><creatorcontrib>Tamura, Yasushi</creatorcontrib><creatorcontrib>Fukaya, Masahiro</creatorcontrib><creatorcontrib>Kensler, Thomas W</creatorcontrib><creatorcontrib>Iijima, Miho</creatorcontrib><creatorcontrib>Sesaki, Hiromi</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids 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>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 Journal of cell biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wakabayashi, Junko</au><au>Zhang, Zhongyan</au><au>Wakabayashi, Nobunao</au><au>Tamura, Yasushi</au><au>Fukaya, Masahiro</au><au>Kensler, Thomas W</au><au>Iijima, Miho</au><au>Sesaki, Hiromi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>dynamin-related GTPase Drp1 is required for embryonic and brain development in mice</atitle><jtitle>The Journal of cell biology</jtitle><addtitle>J Cell Biol</addtitle><date>2009-09-21</date><risdate>2009</risdate><volume>186</volume><issue>6</issue><spage>805</spage><epage>816</epage><pages>805-816</pages><issn>0021-9525</issn><eissn>1540-8140</eissn><coden>JCLBA3</coden><abstract>The dynamin-related guanosine triphosphatase Drp1 mediates the division of mitochondria and peroxisomes. To understand the in vivo function of Drp1, complete and tissue-specific mouse knockouts of Drp1 were generated. Drp1-null mice die by embryonic day 11.5. This embryonic lethality is not likely caused by gross energy deprivation, as Drp1-null cells showed normal intracellular adenosine triphosphate levels. In support of the role of Drp1 in organelle division, mitochondria formed extensive networks, and peroxisomes were elongated in Drp1-null embryonic fibroblasts. Brain-specific Drp1 ablation caused developmental defects of the cerebellum in which Purkinje cells contained few giant mitochondria instead of the many short tubular mitochondria observed in control cells. In addition, Drp1-null embryos failed to undergo developmentally regulated apoptosis during neural tube formation in vivo. However, Drp1-null embryonic fibroblasts have normal responses to apoptotic stimuli in vitro, suggesting that the apoptotic function of Drp1 depends on physiological cues. These findings clearly demonstrate the physiological importance of Drp1-mediated organelle division in mice.</abstract><cop>United States</cop><pub>The Rockefeller University Press</pub><pmid>19752021</pmid><doi>10.1083/jcb.200903065</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adenosine triphosphatase Adenosine Triphosphate - metabolism Animals Antibodies Apoptosis Brain Cells, Cultured Cellular biology Cerebellum Cerebellum - embryology Cerebellum - enzymology Cerebellum - ultrastructure Cytochromes Dynamins Embryology Embryos Fibroblasts - enzymology Fibroblasts - ultrastructure Gestational Age Giant cells Giant Cells - enzymology Giant Cells - ultrastructure GTP Phosphohydrolases - deficiency GTP Phosphohydrolases - genetics GTP Phosphohydrolases - metabolism Mice Mice, Inbred C57BL Mice, Knockout Microtubule-Associated Proteins - deficiency Microtubule-Associated Proteins - genetics Microtubule-Associated Proteins - metabolism Mitochondria Mitochondria - enzymology Mitochondria - ultrastructure Mitochondrial Size Myocytes, Cardiac - enzymology Myocytes, Cardiac - ultrastructure Neurons Organelle Shape Organogenesis Peroxisomes Peroxisomes - enzymology Peroxisomes - ultrastructure Purkinje Cells - diagnostic imaging Purkinje Cells - enzymology Rodents Trophoblasts - enzymology Trophoblasts - ultrastructure Ultrasonography |
title | dynamin-related GTPase Drp1 is required for embryonic and brain development in mice |
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