Regulatory mechanism of mitochondria dynamics during progression of cardiac reverse remodeling
| Project/Area Number |
15K09140
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Cardiovascular medicine
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
HIKOSO Shungo 大阪大学, 医学系研究科, 寄附講座准教授 (30423164)
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| Research Collaborator |
MURAKAWA Tomokazu
YASUI Hiroki
UEDA Hiromichi
AKAZAWA Yasuhiro
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| 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 / ミトコンドリア |
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| 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.
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Report
(4 results)
Research Products
(15 results)
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[Journal Article] FKBP8 protects the heart from hemodynamic stress by preventing the accumulation of misfolded proteins and endoplasmic reticulum-associated apoptosis in mice.2018
Author(s)
Misaka T, Murakawa T, Nishida K, Omori Y, Taneike M, Omiya S, Molenaar C, Uno Y, Yamaguchi O, Takeda J, Shah AM, Otsu K.
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Journal Title
J Mol Cell Cardiol.
Volume: 114
Pages: 93-104
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] mTOR Hyperactivation by Ablation of Tuberous Sclerosis Complex 2 in the Mouse Heart Induces Cardiac Dysfunction with the Increased Number of Small Mitochondria Mediated through the Down-Regulation of Autophagy.2016
Author(s)
Taneike M, Nishida K, Omiya S, Zarrinpashneh E, Misaka T, Kitazume-Taneike R, Austin R, Takaoka M, Yamaguchi O, Gambello MJ, Shah AM, Otsu K.
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Journal Title
PLoS One
Volume: 11
Issue: 3
Pages: e0152628-e0152628
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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.
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Journal Title
Nat Commun.
Volume: 6
Issue: 1
Pages: 7527-7527
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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