Mitochondrial fission factor Drp1 is essential for embryonic development and synapse formation in mice
| Autor: | Maki Maeda, Katsuyoshi Mihara, Yu-ichi Goto, Akihiro Jofuku, Naoko Taguchi, Satoshi O. Suzuki, Hidetaka Morinaga, Naotada Ishihara, Keiji Masuda, Sadaki Yokota, Ryoichi Takayanagi, Hiroki Kato, Hidenori Otera, Masatoshi Nomura, Yae Nakanishi, Ikuya Nonaka |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Male
endocrine system Mitochondrial fission factor Time Factors Blotting Western Embryonic Development Mammalian embryology Mitochondrion Biology Mitochondrial apoptosis-induced channel Cell Line GTP Phosphohydrolases Mitochondrial Proteins Mice DNM1L Animals Cells Cultured Mice Knockout Neurons Brain Cytochromes c Cell Biology Fibroblasts Embryo Mammalian Immunohistochemistry Mitochondria Cell biology Mice Inbred C57BL Luminescent Proteins Microscopy Electron Animals Newborn Microscopy Fluorescence mitochondrial fusion Synapses Forebrain Female Mitochondrial fission |
| Zdroj: | Nature Cell Biology. 11:958-966 |
| ISSN: | 1476-4679 1465-7392 |
| DOI: | 10.1038/ncb1907 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|