Cited by 667Mitochondrial Function and PathologyAutophagy in Disease and TherapyCell death mechanisms and regulation

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

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Wakabayashi, Junko, Zhang, Zhongyan, Wakabayashi, Nobunao, Tamura, Yasushi, Fukaya, Masahiro, Kensler, Thomas W., Iijima, Miho, Sesaki, Hiromi·2009·Journal of Cell Biology

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.

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Authors
Wakabayashi, J., Zhang, Z., Wakabayashi, N., Tamura, Y., Fukaya, M., Kensler, T. W., Iijima, M., & Sesaki, H.
Affiliations
  • Johns Hopkins University (US)
  • Hokkaido University (JP)
Corresponding author
Sesaki, Hiromi
Venue
Journal of Cell Biology
Published
2009-09-14
Volume
186
Issue
6
Pages
805-816
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
OpenAlex
W2107257651
Cited by
667
References
78
Citations by year
2026: 19 · 2025: 39 · 2024: 42 · 2023: 36 · 2022: 40 · 2021: 52 · 2020: 55 · 2019: 43 · 2018: 52 · 2017: 49 · 2016: 33 · 2015: 42 · 2014: 38 · 2013: 30 · 2012: 42
FWCI
12.87
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords
Drp1, dynamin-related GTPase, mitochondrial fission, peroxisome division, embryonic lethality, brain development, cerebellum, Purkinje cells, giant mitochondria, developmental apoptosis, neurulation, ATP levels, organelle division
MeSH terms
Adenosine Triphosphate, Animals, Cells, Cultured, Cerebellum, Fibroblasts, Gestational Age, Mice, Inbred C57BL, Microtubule-Associated Proteins, Mitochondria, Purkinje Cells, Trophoblasts, Ultrasonography, Giant Cells, Apoptosis, Mice, Knockout, GTP Phosphohydrolases, Peroxisomes, Myocytes, Cardiac, Dynamins, Organogenesis, Mice, Organelle Shape, Mitochondrial Size

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