Molecular mechanism of mitochondrial fission

2015 Fiscal Year Final Research Report

• Project/Area Number: 25440088
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cell biology
• Research Institution: Kyushu University
• Principal Investigator: Otera Hidenori 九州大学, 医学(系)研究科(研究院), 助教 (40380612)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: ミトコンドリア / アポトーシス / オルガネラ形態

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.

Free Research Field

分子細胞生物学