2025-08-21 理化学研究所
人工アセチル化酵素分子eMATによる細胞老化の仕組み
<関連情報>
- https://www.riken.jp/press/2025/20250821_2/index.html
- https://www.cell.com/iscience/fulltext/S2589-0042(25)01494-4
エンジニアードアセチルトランスフェラーゼによるミトコンドリアの過アセチル化は細胞老化を促進する Mitochondrial hyper-acetylation induced by an engineered acetyltransferase promotes cellular senescence
Tadahiro Shimazu ∙ Ayane Kataoka ∙ Takehiro Suzuki ∙ Naoshi Dohmae ∙ Yoichi Shinkai
iScience Published:July 29, 2025
DOI:https://doi.org/10.1016/j.isci.2025.113233
Highlights
- Engineered eMAT induces global lysine acetylation in mitochondria
- 74% of eMAT targets overlap with known mitochondrial acetyl-proteins
- eMAT-driven acetylation inhibits metabolism and promotes senescence
- SIRT3 reverses eMAT effects and protects against cellular senescence
Summary
Protein acetylation plays crucial roles in diverse biological functions, including mitochondrial metabolism. Although SIRT3 catalyzes the removal of acetyl groups in mitochondria, the addition of the acetyl groups is thought to be primarily controlled in an enzyme-independent manner due to the absence of potent acetyltransferases. In this study, we developed an engineered mitochondria-localized acetyltransferase, named engineered mitochondrial acetyltransferase (eMAT). eMAT localized in the mitochondrial matrix and introduced robust global protein lysine acetylation, including 413 proteins with 1,119 target lysine residues. Notably, 74% of the acetylated proteins overlapped with previously known acetylated proteins, indicating that the eMAT-mediated acetylation system is physiologically relevant. Functionally, eMAT negatively regulated mitochondrial energy metabolism, inhibited cell growth, and promoted cellular senescence, suggesting that mitochondrial hyper-acetylation drives metabolic inhibition and cellular senescence. SIRT3 counteracted eMAT-induced acetylation and metabolic inhibition, restored cell growth, and protected cells from senescence, highlighting the contribution of SIRT3 in maintaining energy metabolism and preventing cellular senescence.
