Elucidation of molecular mechanism of autophagy and lipid metabolism supporting soundness of organelles
| Project/Area Number |
16K07689
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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 |
Applied biochemistry
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| Research Institution | Kyoto University |
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Principal Investigator |
Oku Masahide 京都大学, 農学研究科, 助教 (10511230)
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| Research Collaborator |
ABE Masato
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | オートファジー / カルジオリピン / 脂肪滴 / ペルオキシソーム / ミクロオートファジー / 液胞 |
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| Outline of Final Research Achievements |
The aim of this project was to elucidate the molecular mechanism underlying maintenance of organelles functionality. In particular, the mitochondrion emitting reactive-oxygen species (ROS) and the lipid droplet, a major storage site of neutral lipids, were chosen as the objects of the studies on the lipid dynamics and autophagy system.
Through this project, the substrate specificity of a yeast enzyme termed tafazzin was revealed as a determinant of the composition of fatty acid moiety within the mitochondrial lipid, cardiolipin. As with the lipid droplet, the role of an autophagy-related protein, Atg8, was uncovered in counteracting degradation of neutral lipids through lipolysis. In addition, a new type of autophagy (microautophagy) was discovered that is dependent on the so-called ESCRT proteins.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、カルジオリピンがいかにして不飽和脂肪酸鎖を多く含むリン脂質として合成されるのか、という問いについて、タファジンという、ヒトの疾患にも関与する酵素の基質特異性から答えを得られたことが大きな意義である。また、脂肪滴の量調節は細胞内の中性脂質量も左右する重要性をもつが、オートファジーに機能するタンパク質がこの量調節に機能するという発見は、哺乳類細胞にも共通するもので普遍的重要性を持つと考えられる。さらに、リソソーム（液胞）膜が直接変形して分解対象を取り込むミクロオートファジーの新たな分子機構を提示することができたことは、オートファジーの多様性理解に大きく貢献したと考えている。
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Report
(4 results)
Research Products
(19 results)
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[Journal Article] Evolution from covalent conjugation to non-covalent interaction in the ubiquitin-like ATG12 system2019
Author(s)
Pang, Y., Yamamoto, H., Sakamoto, H., Oku, M., Mutungi, J.K., Sahani, M.H., Kurikawa, Y., Kita, K., Noda, N.N., Sakai, Y., Jia, H., Mizushima, N.
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Journal Title
Nat. Struct. Mol. Biol.
Volume: 26
Issue: 4
Pages: 289-296
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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