Small molecule agonist of mitochondrial fusion repairs mitochondrial dysfunction
文献类型：期刊论文
| 作者 | Guo,Yingjie; Zhang,Huan; Yan,Chen; Shen,Birong; Zhang,Yue ; Guo,Xiangyang; Sun,Sha; Yu,Fan; Yan,Jiayun; Liu,Ronghe
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| 刊名 | NATURE CHEMICAL BIOLOGY
 |
| 出版日期 | 2023 |
| 卷号 | 19期号:4页码:468-+ |
| 关键词 | ENDOPLASMIC-RETICULUM PROVIDE INSIGHT MITOFUSIN 2 MFN1 DYNAMICS REQUIRES DEFECTS FISSION CELLS |
| ISSN号 | 1552-4469 |
| DOI | 10.1038/s41589-022-01224-y |
| 英文摘要 | Membrane dynamics are important to the integrity and function of mitochondria. Defective mitochondrial fusion underlies the pathogenesis of multiple diseases. The ability to target fusion highlights the potential to fight life-threatening conditions. Here we report a small molecule agonist, S89, that specifically promotes mitochondrial fusion by targeting endogenous MFN1. S89 interacts directly with a loop region in the helix bundle 2 domain of MFN1 to stimulate GTP hydrolysis and vesicle fusion. GTP loading or competition by S89 dislodges the loop from the GTPase domain and unlocks the molecule. S89 restores mitochondrial and cellular defects caused by mitochondrial DNA mutations, oxidative stress inducer paraquat, ferroptosis inducer RSL3 or CMT2A-causing mutations by boosting endogenous MFN1. Strikingly, S89 effectively eliminates ischemia/reperfusion (I/R)-induced mitochondrial damage and protects mouse heart from I/R injury. These results reveal the priming mechanism for MFNs and provide a therapeutic strategy for mitochondrial diseases when additional mitochondrial fusion is beneficial. |
| 学科主题 | Biochemistry & Molecular Biology |
| WOS记录号 | WOS:000913493200003 |
| 源URL | [http://ir.kib.ac.cn/handle/151853/75538]  |
| 专题 | 中国科学院昆明植物研究所 |
| 推荐引用方式 GB/T 7714 | Guo,Yingjie,Zhang,Huan,Yan,Chen,et al. Small molecule agonist of mitochondrial fusion repairs mitochondrial dysfunction[J]. NATURE CHEMICAL BIOLOGY,2023,19(4):468-+. |
| APA | Guo,Yingjie.,Zhang,Huan.,Yan,Chen.,Shen,Birong.,Zhang,Yue.,...&Chen,Quan.(2023).Small molecule agonist of mitochondrial fusion repairs mitochondrial dysfunction.NATURE CHEMICAL BIOLOGY,19(4),468-+. |
| MLA | Guo,Yingjie,et al."Small molecule agonist of mitochondrial fusion repairs mitochondrial dysfunction".NATURE CHEMICAL BIOLOGY 19.4(2023):468-+. |
入库方式： OAI收割
来源：昆明植物研究所
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