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

研究成果: Contribution to journalArticle査読

655 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)958-966
ページ数9
ジャーナルNature Cell Biology
11
8
DOI
出版ステータス出版済み - 2009

All Science Journal Classification (ASJC) codes

  • 細胞生物学

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