Mitochondrial fission factor Drp1 is essential for embryonic development and synapse formation in mice

Naotada Ishihara, Masatoshi Nomura, Akihiro Jofuku, Hiroki Kato, Satoshi Suzuki, Keiji Masuda, Hidenori Otera, Yae Nakanishi, Ikuya Nonaka, Yu Ichi Goto, Naoko Taguchi, Hidetaka Morinaga, Maki Maeda, Ryoichi Takayanagi, Sadaki Yokota, Katsuyoshi Mihara

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Abstract

Mitochondrial morphology is dynamically controlled by a balance between fusion and fission. The physiological importance of mitochondrial fission in vertebrates is less clearly defined than that of mitochondrial fusion. Here we show that mice lacking the mitochondrial fission GTPase Drp1 have developmental abnormalities, particularly in the forebrain, and die after embryonic day 12.5. Neural cell-specific (NS) Drp1-/- mice die shortly after birth as a result of brain hypoplasia with apoptosis. Primary culture of NS-Drp1-/- mouse forebrain showed a decreased number of neurites and defective synapse formation, thought to be due to aggregated mitochondria that failed to distribute properly within the cell processes. These defects were reflected by abnormal forebrain development and highlight the importance of Drp1-dependent mitochondrial fission within highly polarized cells such as neurons. Moreover, Drp1-/- murine embryonic fibroblasts and embryonic stem cells revealed that Drp1 is required for a normal rate of cytochrome c release and caspase activation during apoptosis, although mitochondrial outer membrane permeabilization, as examined by the release of Smac/Diablo and Tim8a, may occur independently of Drp1 activity.

Original languageEnglish
Pages (from-to)958-966
Number of pages9
JournalNature Cell Biology
Volume11
Issue number8
DOIs
Publication statusPublished - Jul 6 2009

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Mitochondrial Dynamics
Synapses
Embryonic Development
Prosencephalon
Apoptosis
Primary Cell Culture
GTP Phosphohydrolases
Mitochondrial Membranes
Neurites
Embryonic Stem Cells
Caspases
Cytochromes c
Vertebrates
Mitochondria
Fibroblasts
Parturition
Neurons
Brain

All Science Journal Classification (ASJC) codes

  • Cell Biology

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Mitochondrial fission factor Drp1 is essential for embryonic development and synapse formation in mice. / Ishihara, Naotada; Nomura, Masatoshi; Jofuku, Akihiro; Kato, Hiroki; Suzuki, Satoshi; Masuda, Keiji; Otera, Hidenori; Nakanishi, Yae; Nonaka, Ikuya; Goto, Yu Ichi; Taguchi, Naoko; Morinaga, Hidetaka; Maeda, Maki; Takayanagi, Ryoichi; Yokota, Sadaki; Mihara, Katsuyoshi.

In: Nature Cell Biology, Vol. 11, No. 8, 06.07.2009, p. 958-966.

Research output: Contribution to journalArticle

Ishihara, N, Nomura, M, Jofuku, A, Kato, H, Suzuki, S, Masuda, K, Otera, H, Nakanishi, Y, Nonaka, I, Goto, YI, Taguchi, N, Morinaga, H, Maeda, M, Takayanagi, R, Yokota, S & Mihara, K 2009, 'Mitochondrial fission factor Drp1 is essential for embryonic development and synapse formation in mice', Nature Cell Biology, vol. 11, no. 8, pp. 958-966. https://doi.org/10.1038/ncb1907
Ishihara, Naotada ; Nomura, Masatoshi ; Jofuku, Akihiro ; Kato, Hiroki ; Suzuki, Satoshi ; Masuda, Keiji ; Otera, Hidenori ; Nakanishi, Yae ; Nonaka, Ikuya ; Goto, Yu Ichi ; Taguchi, Naoko ; Morinaga, Hidetaka ; Maeda, Maki ; Takayanagi, Ryoichi ; Yokota, Sadaki ; Mihara, Katsuyoshi. / Mitochondrial fission factor Drp1 is essential for embryonic development and synapse formation in mice. In: Nature Cell Biology. 2009 ; Vol. 11, No. 8. pp. 958-966.
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