Regulatory mechanism of mitochondria dynamics during progression of cardiac reverse remodeling

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09140
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Osaka University
• Principal Investigator: Yamaguchi Osamu 大阪大学, 医学系研究科, 准教授 (90467580)
• Co-Investigator(Renkei-kenkyūsha): HIKOSO Shungo 大阪大学, 医学系研究科, 寄附講座准教授 (30423164)
• Research Collaborator: MURAKAWA Tomokazu ; YASUI Hiroki ; UEDA Hiromichi ; AKAZAWA Yasuhiro
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: オートファジー / 心不全 / 心肥大 / 逆リモデリング / ミトコンドリアダイナミクス

Outline of Final Research Achievements

Although cardiac reverse remodeling involving regression of cardiac hypertrophy occurs after control of etiological factors, the molecular mechanisms remain to be clarified. We hypothesized that autophagic degradation of mitochondria and mitochondrial fusion/fission play an important role during reverse remodeling. We identified Bcl2-L-13 as a mitophagy receptor on outer mitochondrial membrane. Bcl2-L-13 binds to LC3 through the WXXI motif and induces mitochondrial fragmentation and mitophagy not only in HEK293 cells but in rat neonatal cardiomyocytes. The BH domains are important for the fragmentation, while the WXXI motif facilitates mitophagy. Rubicon is thought to negatively regulate autophagic machinery. We generated cardiac-specific deficient mice of Bcl2-L-13 and Rubicon.

Free Research Field

循環器内科