| Project/Area Number |
21770214
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Cell biology
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| Research Institution | Kyushu University |
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Principal Investigator |
OTERA Hidenori Kyushu University, 医学研究院, 助教 (40380612)
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| Project Period (FY) |
2009 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2009: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 生体膜 / ミトコンドリア / 高分子量GTPase / 膜ダイナミズム / アポトーシス |
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| Research Abstract |
Cytoplasmic dynamin-related GTPase Drp1 is recruited to mitochondria and mediates mitochondrial fission. Although mitochondrial outer membrane (MOM) protein Fis 1 is thought to be a Dip 1 receptor, this has not been confirmed. To analyze the mechanism of Drp 1 recruitment, we manipulated expression of mitochondria] fission and fusion proteins and demonstrated that (i) mitochondrial fission factor (Mff)-knockdown released the Drp 1 foci from MOM accompanied by network extension, while Mff-overexpression stimulated mitochondrial recruitment of Drpl accompanied by mitochondrial fission ; (ii) Mff-dependent mitochondrial fission proceeded independent of Fisl ; (iii) Mff mutant with plasma membrane-targeted CAAX motif directed Drpl to the target membrane ; (iv) Mff and Drpl physically interacted in vitro and in vivo ; (v) exogenous stimuli-induced mitochondrial fission and apoptosis were compromised by knockdown of Drp1 and Mff, but not Fisl ; and (vi) conditional knockout of Fis l in colon carcinoma cells revealed that it is dispensable for mitochondrial fission. Thus, Mff, but not hFis 1, functions as an essential factor in mitochondrial recruitment of Drp 1.
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