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ORIGINAL RESEARCH article

Front. Med.

Sec. Translational Medicine

Volume 12 - 2025 | doi: 10.3389/fmed.2025.1573230

Perilipin 5 alleviates ferroptosis of cardiomyocytes by targeting USP10-p53-TfR proteasome-dependent degradation

Provisionally accepted
Jianqiao  ZhaoJianqiao Zhao1Jiacheng  ShuiJiacheng Shui2Qiyao  XuQiyao Xu1Xindong  WAngXindong WAng1Yuehong  ShenYuehong Shen1Chengyuan  LiuChengyuan Liu3Jianping  ShenJianping Shen4*
  • 1Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
  • 2China Academy of Chinese Medical Sciences, Beijing, Beijing Municipality, China
  • 3Eye Hospital of China Academy of Chinese Medical Sciences, Beijing, China
  • 4Affliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China

The final, formatted version of the article will be published soon.

Introduction: Perilipin 5 (PLIN5) is a key protein attached to lipid droplets that plays a critical role in cellular lipid metabolism. However, its involvement in cardiomyocyte ferroptosis has not been fully elucidated. This study explored the impact of PLIN5 on ferroptosis in H9c2 cells and a rat model of myocardial infarction (MI).: H9c2 cells were treated with H2O2 and Erastin, while the rat model of MI was established by ligating the left anterior descending coronary artery. Results: We found that after MI, cardiac subcellular iron levels increased and the expression of PLIN5 decreased. Overexpression of PLIN5 reduced lipid peroxidation, enhanced ferroptosis resistance, decreased iron accumulation, and lowered TfR expression. Additionally, there was an interaction between PLIN5 and ubiquitin-specific peptidase 10 (USP10). PLIN5 increased the ubiquitination of p53. USP10 and MG-132 blocked the regulatory effect of PLIN5 on TfR expression. Overexpression of USP10 weakened the inhibitory effect of PLIN5 on ferroptosis. In vivo experiments showed that overexpression of PLIN5 significantly reduced ferroptosis in the infarcted myocardium. Discussion: PLIN5 may exert cardioprotective effects by regulating the USP10 and p53-TfR axis.

Keywords: PLIN5, ferroptosis, TfR, iron accumulation, Myocardial Infarction

Received: 08 Feb 2025; Accepted: 11 Jun 2025.

Copyright: © 2025 Zhao, Shui, Xu, WAng, Shen, Liu and Shen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Jianping Shen, Affliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China

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