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PMID: 19578372 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Nature cell biology ·Vol. 11 ·No. 8 ·2009-08-00 ·Pages 958-66

Ishihara N, Nomura M, Jofuku A, Kato H, Suzuki SO, Masuda K, Otera H, Nakanishi Y, Nonaka I, Goto Y, Taguchi N, Morinaga H, Maeda M, Takayanagi R, Yokota S, Mihara K

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.

MeSH Terms
Animals Animals, Newborn Blotting, Western Brain/cytology,embryology,metabolism Cell Line Cells, Cultured Cytochromes c/metabolism Embryo, Mammalian/cytology,embryology,metabolism Embryonic Development/genetics,physiology Female Fibroblasts/cytology,metabolism,ultrastructure GTP Phosphohydrolases/genetics,metabolism Immunohistochemistry Luminescent Proteins/genetics,metabolism Male Mice Mice, Inbred C57BL Mice, Knockout Microscopy, Electron Microscopy, Fluorescence Mitochondria/enzymology,ultrastructure Mitochondrial Proteins/genetics,metabolism Neurons/cytology,metabolism Synapses/enzymology,metabolism,ultrastructure Time Factors
Chemicals
Luminescent Proteins Mitochondrial Proteins Cytochromes c GTP Phosphohydrolases
Authors & Affiliations
16 authors, click to expand affiliations / ORCID
Ishihara Naotada
Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
Nomura Masatoshi
Jofuku Akihiro
Kato Hiroki
Suzuki Satoshi O
Masuda Keiji
Otera Hidenori
Nakanishi Yae
Nonaka Ikuya
Goto Yu-Ichi
Taguchi Naoko
Morinaga Hidetaka
Maeda Maki
Takayanagi Ryoichi
Yokota Sadaki
Mihara Katsuyoshi
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Article Info
Journal
Nature cell biology
Abbr.
Nat Cell Biol
ISSN
1476-4679
DOI
10.1038/ncb1907
Published
2009-08-00
Epub
2009-00-05
Pages
958-66
Language
English
Region
England
NLM ID
100890575
Subset
IM
External Links
PubMed source DOI: 10.1038/ncb1907 View journal details
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