2012 Fiscal Year Final Research Report
Mechanism of mitochondrial fission: from the initial formation of fission sites to the membrane scission
| Project/Area Number |
23770231
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Cell biology
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2012
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| Keywords | 生体膜 |
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| Research Abstract |
Mitochondrial fission is important for maintaining cellular function, and its dysfunction causes aging, neuronal synaptic loss, and cell death in several human neurologic diseases. The major player of mitochondrial fission is a largely cytosolic member of the dynamin family of GTPases Drp1 in mammals. Endogenous Drp1, observed as dotted structures on mitochondria, was clearly decreased and was dispersed in the cytoplasm in Mff RNAi cells concomitant with mitochondrial network extension. In contrast, Mff overexpression induced mitochondrial fragmentation, concomitant with increased Drp1 recruitment to the mitochondria. These observations indicate that Mff functions as a Drp1 receptor to mediate mitochondrial fission. Drp1 might self-assemble via its ability to homo-oligomerize at Mff-containing foci on the mitochondrial surface, forming spiral structures around the mitochondrial tubules. MiD51/MIEF1 interacts with recombinant Drp1 to inhibit its GTPase activity accompanied by Drp1 oligomerization. In contrast, Mff competes with MiD51/MIEF1 to stimulate Drp1 GTPase activity. Taken together, MiD51/MIEF1 seems to bind oligomerized Drp1 and stabilize them at the surface of the mitochondrial membrane in the GTP-locked state to inhibit mitochondrial fission.
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[Journal Article] Fis1 acts as mitochondrial recruitment factor for TBC1D15 that involved in regulation of mitochondrial morphology.
Author(s)
Onoue K, Jofuku A, Ban-Ishihara R, Ishihara T, Maeda M, Koshiba T, Itoh T, Fukuda M, Otera H, Oka T, Takano H, Mizushima N, Mihara K, Ishihara N.
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Journal Title
DOI
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