2022 Fiscal Year Final Research Report
Mitochondrial energy metabolism abnormalities and cancer malignancy induced by excess Mg ions.
| Project/Area Number |
19K16125
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 44010:Cell biology-related
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| Research Institution | Kyoto University (2022)
Osaka University (2019-2021) |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Keywords | Mg2+ / CNNM / PRL / ATP / ミトコンドリア / がん悪性化 |
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| Outline of Final Research Achievements |
The effects of excessive intracellular accumulation of Mg2+ by suppression of the Mg2+ transporter CNNM, which extrudes intracellular Mg2+, were analysed using cultured cells, C. elegans and the mouce model. In cultured cells, excess intracellular Mg2+ accelerated ATP production in mitochondria, resulting in the overproduction of ROS; in cnnm mutant worms, the augmented ROS caused a shortened lifespan; and in the Cnnm4-deficient mice, intestinal epithelial cells, where CNNM is highly expressed, caused oxidative stress and increased cell proliferation. Excessive accumulation of Mg2+ in cells has been shown to cause cancer malignancy, and this study suggests that ROS are involved in this process.
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| Free Research Field |
細胞生物学
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| Academic Significance and Societal Importance of the Research Achievements |
Mgイオンは細胞にとって必須な物質の一つであり、細胞内のMgイオンレベルは厳密に保たれている。CNNMの抑制による細胞内でMgイオンの過剰蓄積によりROSが過剰産生され、線虫では寿命の短縮、マウスでは腸上皮細胞の異常増殖を引き起こすことを明らかにした。CNNMが進化的に広く保存されていることからも細胞内のMgイオンの過剰蓄積は細胞にとって避けるべき状況であると考えられ、CNNMのような細胞内のMgイオンを排出するトランスポーターが存在することの生物学的重要性が明らかになった。
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