Doxorubicin-Induced Cardiotoxicity Related to Regulation of Mitochondrial-Associated Membranes by PDK4

doi:10.19803/j.1672-8629.20250272

Abstract

Abstract: Objective To analyze the molecular mechanism through which PDK4 regulates Mitochondria-Associated Membranes(MAMs) and explore its potential association with anthracycline-induced cardiotoxicity in order to provide data for developing cardioprotective strategies. Methods By reviewing recent literature, the role of PDK4 in MAMs and its potential involvement in anthracycline-induced cardiotoxicity was explored. Results There were complicated interactions between PDK4, MAMs, and anthracycline-induced cardiotoxicity, primarily manifested as energy metabolism disorders, oxidative stress, apoptosis, and calcium homeostasis imbalance. These interactions played a significant role in the progression of anthracycline-induced cardiotoxicity. Conclusion Overexpression of PDK4 can, above all, disrupt calcium homeostasis mediated by MAMs, leading to mitochondrial calcium overload and consequently exacerbating anthracycline-induced cardiotoxicity. This study can offer novel insights and help identify potential therapeutic targets for developing protective strategies against anthracycline-associated cardiotoxicity.

Key words: Anthracyclines, PDK4, Cardiotoxicity, Mitoch-ondria-Associated Membranes(MAMS), Mitochondrial Dysfunction, Calcium Homeostasis

CLC Number:

R994.13
R972

SHI Yanlei, ZHANG Bing, WANG Yu, XU Zhuoxin, TIAN Min, MENG Min, SA Rina. Doxorubicin-Induced Cardiotoxicity Related to Regulation of Mitochondrial-Associated Membranes by PDK4[J]. Chinese Journal of Pharmacovigilance, 2025, 22(8): 863-868.

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https://zgywjj.magtechjournal.com/EN/Y2025/V22/I8/863

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