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
Hauptverfasser: Wakabayashi, Junko, Zhang, Zhongyan, Wakabayashi, Nobunao, Tamura, Yasushi, Fukaya, Masahiro, Kensler, Thomas W, Iijima, Miho, Sesaki, Hiromi
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container_end_page 816
container_issue 6
container_start_page 805
container_title The Journal of cell biology
container_volume 186
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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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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