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細胞膜損傷依存的な細胞老化におけるカルシウムイオン動態とオルガネラ相互作用の役割
https://doi.org/10.15102/0002000456
https://doi.org/10.15102/00020004568f44703d-b7f5-48ad-a840-3655b2948bb9
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SudaKojiroFulltext.pdf (2.8 MB)
Download is available from 2025/4/3.
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SudaKojiroExamAbstract.pdf (48 KB)
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SudaKojiroSummary.pdf (542 KB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||
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| 公開日 | 2024-04-16 | |||||||
| タイトル | ||||||||
| タイトル | 細胞膜損傷依存的な細胞老化におけるカルシウムイオン動態とオルガネラ相互作用の役割 | |||||||
| 言語 | ja | |||||||
| タイトル | ||||||||
| タイトル | The Role of Calcium Ion Dynamics and Inter-Organelle Communication During Plasma Membrane Damage-Dependent Cellular Senescence | |||||||
| 言語 | en | |||||||
| 言語 | ||||||||
| 言語 | eng | |||||||
| キーワード | ||||||||
| 主題Scheme | Other | |||||||
| 主題 | Organelle contact sites | Ca2+ dynamics | cellular senescence | |||||||
| 資源タイプ | ||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||
| 資源タイプ | doctoral thesis | |||||||
| ID登録 | ||||||||
| ID登録 | 10.15102/0002000456 | |||||||
| ID登録タイプ | JaLC | |||||||
| アクセス権 | ||||||||
| アクセス権 | open access | |||||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||
| 著者 |
須田 晃治郎
× 須田 晃治郎
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| 著者 (英) |
Suda, Kojiro
× Suda, Kojiro
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| 抄録 | ||||||||
| 内容記述タイプ | Abstract | |||||||
| 内容記述 | Cellular senescence is a stable cell cycle arrest that contributes to a variety of physiological and pathological processes in vivo, including organismal aging, wound healing, and cancer. Accumulating evidence suggests that elimination of senescent cells ameliorates age-related pathologies. In vitro, various stresses, including oxidative stress, oncogene activation, telomere shortening, and DNA damage, induce cellular senescence via the DNA damage response. However, the triggers of cellular senescence in vivo remain controversial. Here, I show that cellular senescence is induced by physiologically and pathologically occurring plasma membrane damaging stimuli such as mechanical injury and pore-forming toxins in normal human fibroblasts in vitro. I found that Ca2+ influx into the cytosol following plasma membrane damage is necessary and sufficient for the induction of plasma membrane damage-dependent senescence. Live cell imaging revealed that Ca2+ entering the cytosol is immediately incorporated by the endoplasmic reticulum (ER). Subsequently, mitochondrial Ca2+ levels rise steadily, suggesting Ca2+ transport from the ER to the mitochondria via their contact sites. I observed an increase in mitochondrial oxidative stress, and attenuation of oxidative stress with antioxidants suppressed plasma membrane damage-dependent senescence. These results suggest that mitochondrial dysfunction due to Ca2+ accumulation induces plasma membrane damage-dependent senescence. I also found that Ca2+ transport from the ER to the mitochondria is necessary to maintain cytosolic Ca2+ levels and cell survival after plasma membrane damage. Proteomic analysis identified the proteins that mediate the ER-mitochondria contact. This study highlights an underappreciated subtype of cellular senescence, plasma membrane damage-dependent senescence, and provides mechanistic insights into Ca2+ dynamics based on plasma membrane damage-triggered inter-organelle communication. | |||||||
| 言語 | en | |||||||
| 口頭試問日 | ||||||||
| 値 | 2024-03-13 | |||||||
| 学位授与年月日 | ||||||||
| 学位授与年月日 | 2024-03-31 | |||||||
| 学位名 | ||||||||
| 学位名 | Doctor of Philosophy | |||||||
| 学位授与番号 | ||||||||
| 学位授与番号 | 甲第148号 | |||||||
| 学位授与機関 | ||||||||
| 学位授与機関識別子Scheme | kakenhi | |||||||
| 学位授与機関識別子 | 38005 | |||||||
| 学位授与機関名 | Okinawa Institute of Science and Technology Graduate University | |||||||
| 著者版フラグ | ||||||||
| 出版タイプ | VoR | |||||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||
| 権利 | ||||||||
| 権利情報 | © 2024 The Author. | |||||||
