2. Academic Validation
  3. Overexpression of hnRNPK and inhibition of cytoplasmic translocation ameliorate lipid disorder in doxorubicin-induced cardiomyopathy via PINK1/Parkin-mediated mitophagy

Overexpression of hnRNPK and inhibition of cytoplasmic translocation ameliorate lipid disorder in doxorubicin-induced cardiomyopathy via PINK1/Parkin-mediated mitophagy

  • Free Radic Biol Med. 2025 Apr:231:94-108. doi: 10.1016/j.freeradbiomed.2025.02.021.
Qian Xu 1,  Xuehua Wang 1,  Jing Hu 2,  Ya Wang 1,  Shuai Lu 3,  Jingjie Xiong 1,  Han Li 1,  Ni Xiong 1,  YanLing Huang 1,  Yan Wang 4,  Zhaohui Wang 5
Affiliations

Affiliations

  • 1 Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China; Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China; Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China.
  • 2 Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China.
  • 3 Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • 4 Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China; Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China; Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China. Electronic address: tomato82@126.com.
  • 5 Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China; Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China; Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China. Electronic address: wuxiaohongtian@163.com.
PMID: 39984063 DOI: 10.1016/j.freeradbiomed.2025.02.021
Abstract

Lipid metabolism has been identified as a potential target for the treatment of doxorubicin-induced cardiomyopathy (DIC). Mitochondria, as a central regulator of energy production and utilization, plays a crucial role in this process, and enhancing Mitophagy holds promise in mitigating myocardial damage in DIC. However, the relationship between Mitophagy and lipid metabolism remains unclear, and the key molecules mediating this connection remain to be elucidated. Among these candidates, heterogeneous nuclear ribonucleoprotein K (hnRNPK) emerges as a potential regulator of Mitophagy and metabolism. However, its specific role in DIC remains unclear. In this study, we established chronic DIC models both in vivo and in vitro to assess the relationship between hnRNPK levels, Mitophagy, and lipid metabolism, as well as to evaluate the impact of hnRNPK on cardiac function. Our findings revealed that hnRNPK expression is significantly reduced in the hearts of doxorubicin (DOX)-treated mice. Notably, hnRNPK overexpression improves cardiac function and effectively reduces lipid accumulation by enhancing Mitophagy. Mechanistically, hnRNPK expression was found to be downregulated in DIC, accompanied by its translocation from the nucleus to the cytoplasm, thereby reducing the transcriptional regulation of PINK1. Overexpression of hnRNPK and inhibition of its cytoplasmic translocation alleviates DOX-induced lipid accumulation by regulating the PINK1/Parkin pathway. These findings underscore a previously unrecognized role of hnRNPK in inhibiting lipid accumulation to prevent DIC.

Keywords

Doxorubicin-induced cardiomyopathy; Lipid metabolism; Mitophagy; PINK1/Parkin; Therapeutic target; hnRNPK.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z