The dynamin-related GTPase Drp1 is required for embryonic and brain development in mice
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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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Constitutive DRP1 knockout animals are embryonically lethal, demonstrating that the fission machinery is critical for tissue development and function.
“Constitutive DRP1 knockout animals are embryonically lethal, demonstrating that the fission machinery is critical for tissue development and function [208, 209].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [209]
Conditional ablation of DRP1 in the heart, brain, and skeletal muscle causes lethality.
“Consistent with this crucial role, conditional ablation of DRP1 in the heart, brain, and skeletal muscle causes lethality [196, 198–200, 208, 209].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [209]
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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
- ORCID
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2009-09-14
- Volume
- 186
- Issue
- 6
- Pages
- 805-816
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2753156
- 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
- hybrid
- doi.org
- 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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