2022 Fiscal Year Final Research Report
ATP signaling controlled by mitochondrial dynamics
| Project/Area Number |
20K08921
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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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| Review Section |
Basic Section 54040:Metabolism and endocrinology-related
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| Research Institution | Kurume University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
蓮澤 奈央 久留米大学, 医学部, 助教 (00837908)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | ATP / Mitochondrial dynamics / VNUT / DRP1 / NASH / Purinergic signal / Mitochondrial fission / Autophagy |
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| Outline of Final Research Achievements |
This study elucidated the molecular mechanisms underlying the progression to NASH and cirrhosis following overeating. A key aspect of this process is the regulation of ATP production through the dynamic behavior of mitochondria. Mitochondria, acting as sensors of the organism's energy balance, play a crucial role in modulating ATP synthesis.
When excess energy is supplied to hepatocytes, ATP production within these cells increases, leading to elevated intracellular ATP levels. Consequently, there is a subsequent rise in the secretion of ATP through vesicular nucleotide transporter (VNUT). The activation of purine receptor signaling following extracellular ATP secretion phosphorylates DRP1 and triggers mitochondrial fission. The metabolic product ATP also acts as a DAMP, indicating that purine receptor signaling initiated by VNUT is essential for DRP1-mediated mitochondrial division.
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| Free Research Field |
Endocrinology and metabolism
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| Academic Significance and Societal Importance of the Research Achievements |
高齢化社会を迎え、糖尿病、NASHといった生活習慣病が急増し、その克服は健康寿命の延伸に不可欠である。現代社会における過食、過栄養の結果、蓄積する代謝物に対する自然免疫応答により慢性炎症が引き起こされることがこれら生活習慣病に共通の分子基盤であることが示唆されている。本研究により、ミトコンドリアダイナミクス（代謝）とプリン受容体シグナル（炎症）をつなぐ分子としてVNUTを同定し、代謝物であるATP自身が炎症を惹起する分子機構を明らかにした。この研究成果を基に、VNUTを標的とするNASHを含めた生活習慣病の予防法、治療法開発が進むことが期待される。
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