論文 - 詳細
| RRC ID | 73056 |
|---|---|
| 著者 | Takaine M, Imamura H, Yoshida S. |
| タイトル | High and stable ATP levels prevent aberrant intracellular protein aggregation in yeast. |
| ジャーナル | Elife |
| Abstract |
Adenosine triphosphate (ATP) at millimolar levels has recently been implicated in the solubilization of cellular proteins. However, the significance of this high ATP level under physiological conditions and the mechanisms that maintain ATP remain unclear. We herein demonstrated that AMP-activated protein kinase (AMPK) and adenylate kinase (ADK) cooperated to maintain cellular ATP levels regardless of glucose levels. Single-cell imaging of ATP-reduced yeast mutants revealed that ATP levels in these mutants underwent stochastic and transient depletion, which promoted the cytotoxic aggregation of endogenous proteins and pathogenic proteins, such as huntingtin and α-synuclein. Moreover, pharmacological elevations in ATP levels in an ATP-reduced mutant prevented the accumulation of α-synuclein aggregates and its cytotoxicity. The present study demonstrates that cellular ATP homeostasis ensures proteostasis and revealed that suppressing the high volatility of cellular ATP levels prevented cytotoxic protein aggregation, implying that AMPK and ADK are important factors that prevent proteinopathies, such as neurodegenerative diseases. |
| 巻・号 | 11 |
| 公開日 | 2022-4-19 |
| DOI | 10.7554/eLife.67659 |
| PII | 67659 |
| PMID | 35438635 |
| PMC | PMC9018071 |
| MeSH | AMP-Activated Protein Kinases / metabolism Adenosine Triphosphate / metabolism Adenylate Kinase / metabolism Protein Aggregates* Saccharomyces cerevisiae* / genetics Saccharomyces cerevisiae* / metabolism alpha-Synuclein / genetics alpha-Synuclein / metabolism |
| IF | 7.08 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 49 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 酵母 | |