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个人信息Personal Information
教授 博士生导师 硕士生导师
任职 : Aging，Cancer，Cancer Genetics，Oncology Letters，General Physiology and Biophysics ，Experimental and Therapeutic Medicine，Food & Function, Psychosomatic Medicine Research(Section Editor), Current Pharmaceutical Biotechnology, 赣南医学院学报, 中国生物工程杂志，解剖科学进展
性别：男
毕业院校：清华大学
学历：研究生(博士)毕业
学位：博士生
在职信息：在职
所在单位：基础医学院
入职时间：2021-01-27
学科：遗传学
发育生物学
生物化学与分子生物学
办公地点：山东大学趵突泉校区电镜楼209
联系方式：
Vitamin A and its analogues modulate MUFAs metabolism to improve ferroptosis and aging by direct targeting of ACSL3
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论文名称：Vitamin A and its analogues modulate MUFAs metabolism to improve ferroptosis and aging by direct targeting of ACSL3
发表刊物：Acta Pharmaceutica Sinica B
关键字：Vitamin AAll-trans retinoic acidFerroptosisACSL3Lipid metabolismAcute liver injuryAgingLongevity
摘要：In our screening campaign for novel ferroptosis inhibitors, we identified that vitamin A (VA) and its metabolite all-trans retinoic acid (ATRA) exhibited potent ferroptosis-suppressing activity. Notably, through a combination of biochemical and pharmacological assays, we demonstrated that the anti-ferroptotic effects of VA and ATRA are independent of both antioxidative mechanisms and the canonical RAR/RXR signaling pathway. This conclusion was corroborated by a series of newly synthesized VA analogues. Furthermore, VA and its structural derivatives significantly alleviated ferroptosis-associated pathological phenotypes in murine models. Intriguingly, we discovered a novel function of VA and its analogues, which directly target acyl-CoA synthetase long-chain family member 3 (ACSL3) and enhance its enzymatic activity. This ACSL3-dependent mechanism increases the MUFA/PUFA ratio in phospholipids, thereby preventing lipid peroxidation. Strikingly, we further demonstrated that VA and its analogue D3 [(2E,4E,6E,8E)-N,3,7-trimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraenamide] extend the lifespan of C. elegans in a manner dependent on ACSL3, highlighting the physiological relevance of this pathway in aging. Collectively, our findings unveil a previously unrecognized role for VA and its analogues in modulating lipid metabolism, thereby providing a theoretical basis for their potential application in treating ferroptosis-related diseases and possibly enhancing longevity.
第一作者：Nanxuan Luo,Yijie Xiao,翟义乐
通讯作者：张哲,Shenyou Nie,Haixin Yuan
全部作者：Jie Li,Lijie Lv,Houhua Yin,Fang Lin,Biwen Wan,Ke Zhang,Junchi Hu,Junyan Liu,Yongjun Dang,Yi He,Yahui Zhao
是否译文：否
发表时间：2025-11
收录刊物：SCI
发布期刊链接：https://www.sciencedirect.com/science/article/pii/S2211383525007348
发布时间：2025-11-07