Peer-reviewedCC BYInternational journal of biological sciences
PEGylated nicotinamide mononucleotide targeted ferroptosis in acute kidney injury by suppressing FAR1 palmitoylation in an ACAA1-dependent manner.
8 affiliations
- 1Academy of Military Medical Sciences, Beijing 100850, China.
- 2Pingyuan Laboratory, Henan 453000, China.
- 3Department of Hematology, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100071, China.
- 4Department of Nephrology, Chongqing Key Laboratory of Prevention and Treatment of Kidney Disease, Chongqing Clinical Research Center of Kidney and Urology Diseases, Xinqiao Hospital, Army Medical University (Third Military Medical University), Chongqing 400037, China.
- 5Medical Service Training Center, Chinese PLA General Hospital, Beijing 100853, China.
- 6CapitalBio Technology Corporation, Beijing 101111, China.
- 7Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Beijing 100853, China.
- 8National Key Laboratoty of Kidney Diseases, National Clinical Research Center of Kidney Diseases, Beijing 100853, China.
Abstract
Acute kidney injury (AKI) remains a major health concern globally, with ferroptosis being the most critical pathological change in proximal tubule cells (PTCs). However, no specific pharmacotherapies have been developed yet. Here, by combining databases (in vitro LINCS and in vivo MTDS) covering drug-altered gene profiles with ferroptosis-associated FerrDb, nicotinamide mononucleotide (NMN) was identified to target renal ferroptosis. Furthermore, PEGylation increased the preferential uptake of NMN in mice renal cortex, enhancing its alleviating effect on AKI. Through MALDI-MS-based spatially resolved metabolomics and SEAM analyses, NMN-PEG was found to augment peroxisomal function in PTCs via ACAA1, leading to increased β-oxidation of LCFAs and VLCFAs to mitigate ferroptosis and inflammation. Notably, ACAA1 also suppressed palmitoylation of FAR1 Cys111 to mediate NMN-PEG-improved lipid metabolism. Our study is the first to reveal the renal ferroptosis-targeting role of NMN-PEG and the underlying molecular mechanism, shedding new light on the development of novel AKI therapeutics.
Related
- Nicotinamide Mononucleotide Is Associated with Attenuation of OGD/R-Induced Pro-Inflammatory Programs in Microglia: Transcriptomic Evidence Converging on the NLRP3 Inflammasome and Lipid-Droplet-Related Molecular Signatures
- Nicotinamide Mononucleotide Does Not Prevent Cardiac Hypertrophy but Attenuates Cardiac Stress and Remodeling Markers in Mice Exposed to Intermittent Normobaric Hypoxia
- Fetal hypoxia causes oocyte oxidative stress damage via the Sirt3/Sod2 pathway and can be alleviated by nicotinamide mononucleotide
- Hepatoprotective Effect of Nicotinamide Mononucleotide on High‐Fat Diet‐Induced Non‐Alcoholic Fatty Liver Disease in Mice
- Zdhhc14 promotes pyroptosis in the dorsal root ganglion of oxaliplatin‐induced peripheral neuropathy mice by enhancing GBP5 palmitoylation and suppressing its ubiquitination
BibTeX
@article{yue2026pegylated,
title = {{PEGylated nicotinamide mononucleotide targeted ferroptosis in acute kidney injury by suppressing FAR1 palmitoylation in an ACAA1-dependent manner.}},
author = {Yang Yue and Changdong Zhou and Qingyu Li and Xiaochang Zhang and Hongjun Lin and Ming Niu and Aihong Zhang and Shuiqin Gong and Lijing Yang and Yuke Cui and Hong Chen and Xiaodan Cheng and Jiangbo Li and Qi He and Chenhui Wang and Jian Li and Wen Yang and Jian Bai and Jingqi Shi and Yanze Li and Xing Qin and Xiangmei Chen and Liang Guo and Shengqi Wang},
journal = {International journal of biological sciences},
year = {2026},
month = oct,
doi = {10.7150/ijbs.132234},
url = {https://europepmc.org/article/MED/42909988},
note = {CC BY},
}
RIS
TY - JOUR
TI - PEGylated nicotinamide mononucleotide targeted ferroptosis in acute kidney injury by suppressing FAR1 palmitoylation in an ACAA1-dependent manner.
AU - Yang Yue
AU - Changdong Zhou
AU - Qingyu Li
AU - Xiaochang Zhang
AU - Hongjun Lin
AU - Ming Niu
AU - Aihong Zhang
AU - Shuiqin Gong
AU - Lijing Yang
AU - Yuke Cui
AU - Hong Chen
AU - Xiaodan Cheng
AU - Jiangbo Li
AU - Qi He
AU - Chenhui Wang
AU - Jian Li
AU - Wen Yang
AU - Jian Bai
AU - Jingqi Shi
AU - Yanze Li
AU - Xing Qin
AU - Xiangmei Chen
AU - Liang Guo
AU - Shengqi Wang
PY - 2026
DA - 2026/10/02
JO - International journal of biological sciences
DO - 10.7150/ijbs.132234
UR - https://europepmc.org/article/MED/42909988
AB - Acute kidney injury (AKI) remains a major health concern globally, with ferroptosis being the most critical pathological change in proximal tubule cells (PTCs). However, no specific pharmacotherapies have been developed yet. Here, by combining databases (in vitro LINCS and in vivo MTDS) covering drug-altered gene profiles with ferroptosis-associated FerrDb, nicotinamide mononucleotide (NMN) was identified to target renal ferroptosis. Furthermore, PEGylation increased the preferential uptake of NMN in mice renal cortex, enhancing its alleviating effect on AKI. Through MALDI-MS-based spatially resolved metabolomics and SEAM analyses, NMN-PEG was found to augment peroxisomal function in PTCs via ACAA1, leading to increased β-oxidation of LCFAs and VLCFAs to mitigate ferroptosis and inflammation. Notably, ACAA1 also suppressed palmitoylation of FAR1 Cys111 to mediate NMN-PEG-improved lipid metabolism. Our study is the first to reveal the renal ferroptosis-targeting role of NMN-PEG and the underlying molecular mechanism, shedding new light on the development of novel AKI therapeutics.
SN - 1449-2288
ER -