| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Outline of Final Research Achievements |
Here, we analyzed the functional division of mitochondrial fission receptors with their knockout (KO) cell lines. In marked contrast to Mff-KO cells, MiD49/MiD51-KO and Drp1-KO cells completely resisted cristae-remodeling and cytochrome c release during apoptosis. This phenotype in MiD49/51-KO cells, but not Drp1-KO cells, was completely abolished by treatments that disrupt cristae morphology, such as OPA1-depletion. Unexpectedly, OPA1 oligomers generally thought to resist cytochrome c release by stabilizing the cristae structure were similarly disassembled in both types of cells, revealing that the Drp1-MiD49/51 system limits cristae remodeling. Together, these results indicate that Drp1-dependent mitochondrial fission through MiD49 and MiD51 is epistatic to cristae-remodeling through disassembly of OPA1 oligomers and functions as an essential gatekeeper for intrinsic apoptosis.
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