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PMID: 19752021 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The dynamin-related GTPase Drp1 is required for embryonic and brain development in mice.

The Journal of cell biology ·Vol. 186 ·No. 6 ·2009-09-21 ·Pages 805-16

Wakabayashi J, Zhang Z, Wakabayashi N, Tamura Y, Fukaya M, Kensler TW, Iijima M, Sesaki H

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.

MeSH Terms
Adenosine Triphosphate/metabolism Animals Apoptosis Cells, Cultured Cerebellum/embryology,enzymology,ultrastructure Dynamins Fibroblasts/enzymology,ultrastructure GTP Phosphohydrolases/deficiency,genetics,metabolism Gestational Age Giant Cells/enzymology,ultrastructure Mice Mice, Inbred C57BL Mice, Knockout Microtubule-Associated Proteins/deficiency,genetics,metabolism Mitochondria/enzymology,ultrastructure Mitochondrial Size Myocytes, Cardiac/enzymology,ultrastructure Organelle Shape Organogenesis Peroxisomes/enzymology,ultrastructure Purkinje Cells/diagnostic imaging,enzymology Trophoblasts/enzymology,ultrastructure Ultrasonography
Chemicals
Microtubule-Associated Proteins Adenosine Triphosphate GTP Phosphohydrolases Dnm1l protein, mouse Dynamins
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Wakabayashi Junko
Department of Cell Biology, School of Medicine, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
Zhang Zhongyan
Wakabayashi Nobunao
Tamura Yasushi
Fukaya Masahiro
Kensler Thomas W
Iijima Miho
Sesaki Hiromi
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
1540-8140
DOI
10.1083/jcb.200903065
Published
2009-09-21
Epub
2009-00-14
Pages
805-16
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2753156
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.200903065 PMC Full Text View journal details
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