Exploration for novel therapeutic target of inflammation and heart failure induced by accumulation of mtDNA

• Project/Area Number: 25713031
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Osaka University
• Principal Investigator: Oka Takafumi 大阪大学, 医学(系)研究科(研究院), 特任研究員 (30647285)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥25,350,000 (Direct Cost: ¥19,500,000、Indirect Cost: ¥5,850,000); Fiscal Year 2015: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2014: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000); Fiscal Year 2013: ¥10,790,000 (Direct Cost: ¥8,300,000、Indirect Cost: ¥2,490,000)
• Keywords: ミトコンドリア / 炎症 / 心不全

Outline of Final Research Achievements

We have previously reported that the accumulation of mitochondrial DNA in cardiomyocytes can induce inflammatory response and heart failure. Mitochondria are usually degraded through mitochondria-specific autophagy, mitophagy. In yeast, Atg32 was found to be an essential molecule during mitophagy, however, no functional homologue for Atg32 in mammalian cells had been identified. In this research we investigated a novel molecular mechanism involved in the mitophagy in mammalian cells, and found BCL2L13 as a functional homologue of Atg32. BCL2L13 induced mitochondrial fragmentation and played an important role as a mitophagic receptor on outer mitochondrial membrane.

Research Products

• [Int'l Joint Research] King's College London(英国)
• [Journal Article] Bcl-2-like protein 13 is a mammalian Atg32 homologue that mediates mitophagy and mitochondrial fragmentation. (2015)
  • Author(s): Murakawa T, Yamaguchi O, Hashimoto A, Hikoso S, Takeda T, Oka T, Yasui H, Ueda H, Akazawa Y, Nakayama H, Taneike M, Misaka T, Omiya S, Shah AM, Yamamoto A, Nishida K, Ohsumi Y, Okamoto K, Sakata Y, Otsu K.
  • Journal Title: Nat Commun. Volume: 6 Issue: 1 Pages: 7527-7527
  • DOI: 10.1038/ncomms8527
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Autophagy-mediated degradation is necessary for regression of cardiac hypertrophy during ventricular unloading. (2013)
  • Author(s): Oyabu J, Yamaguchi O, Hikoso S, Takeda T, Oka T, Murakawa T, Yasui H, Ueda H, Nakayama H, Taneike M, Omiya S, Shah AM, Nishida K, Otsu K.
  • Journal Title: Biochemical and Biophysical Research Communication Volume: 441 Issue: 4 Pages: 787-792
  • DOI: 10.1016/j.bbrc.2013.10.135
  • Peer Reviewed