Zhe Zhang
Professor Supervisor of Doctorate Candidates Supervisor of Master's Candidates
Name (Simplified Chinese):张哲
Name (English):Zhe Zhang
Name (Pinyin):Zhang Zhe
Date of Employment:2021-01-27
School/Department:School of Basic Medical Sciences
Administrative Position:Professor
Education Level:Postgraduate (Doctoral)
Business Address:Room 209, Electron Microscopy Building, No.44 Wenhua Xi Road,
Shandong University School of Basic Medical Sciences, Ji'nan, Shandong
250012, P.R.China
Gender:Male
Contact Information:
Degree:Doctor
Status:Employed
Other Post:Aging，Cancer，Cancer Genetics，Oncology Letters，General Physiology and Biophysics ，Experimental and Therapeutic Medicine，Food & Function, Psychosomatic Medicine Research(Section Editor), Current Pharmaceutical Biotechnology, 中国生物工程杂志，解剖科学进展
Alma Mater:Tsinghua University
College:Cheeloo College of Medicine
Discipline:Genetics
Developmental Biology
Biochemistry and Molecular Biology
Hits:
Title of Paper:Vitamin A and its analogues modulate MUFAs metabolism to improve ferroptosis and aging by direct targeting of ACSL3
Journal:Acta Pharmaceutica Sinica B
Key Words:Vitamin A, All-trans retinoic acid, Ferroptosis, ACSL3, Lipid metabolism, Acute liver injury, Aging, Longevity
Summary: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.
First Author:Nanxuan Luo,Yijie Xiao,Yile Zhai
Correspondence Author:Zhe Zhang,Shenyou Nie,Haixin Yuan
All the Authors:Jie Li,Lijie Lv,Houhua Yin,Fang Lin,Biwen Wan,Ke Zhang,Junchi Hu,Junyan Liu,Yongjun Dang,Yi He,Yahui Zhao
Translation or Not:No
Date of Publication:2025-11
Included Journals:SCI
Links to Published Journals:https://www.sciencedirect.com/science/article/pii/S2211383525007348
Release Time:2025-11-07
