Extrusion of mitochondrial contents from lipopolysaccharide-stimulated cells.
| Project/Area Number |
16K09203
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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 |
Legal medicine
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
UNUMA Kana 東京医科歯科大学, 大学院医歯学総合研究科, 講師 (30586425)
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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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | LPS / autophagy / hepatocyte / mitochondria / lysosomal exocytosis; / 敗血症 / 肝臓 / ミトコンドリア障害 / 活性酸素種 / リポポリサッカリド / ミトコンドリア / オートファジー / 一酸化炭素 / プロテオーム / 法医学 |
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| Outline of Final Research Achievements |
In this study, in the liver of sepsis, elimination of damaged mitochondria through the autophagy-lysosome system and increased appearance of mitochondrial DNA in plasma were confirmed. Moeover, we provide evidence for the secretion of mitochondrial proteins and DNA from lipopolysaccharide (LPS)-stimulated rat hepatocytes as well as mouse embryonic fibroblasts (MEFs). The secretion of mitochondrial contents is accompanied by the secretion of proteins that reside in the lumenal space of autolysosomes, but not by a lysosomal membrane protein. The pharmacological inhibition of autophagy and Atg5(-/-) MEFs blocks the secretion of mitochondrial constituents from LPS-stimulated cells. Furthermore, we show that direct exposure of purified mitochondria activates polymorphonuclear leukocytes, as evident by the induction of IL1B/interlekin-1β, a pro-inflammatory cytokine.
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| Academic Significance and Societal Importance of the Research Achievements |
これまで、敗血症病態のヒト血漿中でミトコンドリアに豊富に存在するタンパク発現が増加することなどは知れていたが、多くは逸脱と考えられていた。本研究では、単離白血球に精製ミトコンドリアを曝露したところ、炎症性サイトカインが産生されたことや、細胞膜が破綻しない段階で細胞外に障害ミトコンドリアが確認されたことから、その一部が能動的なメカニズムを介していることが明らかにすることができたのは学術的意義があることと考える。
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Report
(4 results)
Research Products
(27 results)
