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

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

Research output: Contribution to journalArticlepeer-review

813 Citations (Scopus)


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
Issue number8
Publication statusPublished - 2009

All Science Journal Classification (ASJC) codes

  • Cell Biology


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