Work

Methionine is an essential amino acid in doxorubicin-induced cardiotoxicity through modulating mitophagy

Year: 2025

Type: article

Abstract: Doxorubicin (Dox) is a widely used anticancer drug. However, its time- and dose-dependent side effects, particularly severe cardiotoxicity, limit its clinical use. Understanding the molecular mechanisms underlying Dox-induced cardiotoxicity has become a research focus in recent years. Among these, impaired mitophagy which participated in the process of damaged mitochondria clearance, is considered one of the key mechanisms in Dox-induced cardiomyopathy. Methionine (Met) is an essential amino acid that plays a crucial role in various biological processes. This study aims to investigate the role and mechanism of Met in regulating mitophagy in Dox-induced cardiotoxicity. Met deficiency exacerbated Dox-induced cardiotoxicity, primarily by promoting oxidative stress, affecting mitochondria integrity, disrupting autophagy, and thus leading to cardiomyocyte damage and aggravating heart failure. In addition, Met supplementation alleviated Dox-induced cardiotoxicity, via the general control nonderepessible 2 (GCN2) pathway. This study extends our understanding of the relationship between amino acid metabolism and Dox-induced cardiotoxicity, and indicating the Met-GCN2 axis as a promising therapeutic strategy for Dox-induced cardiotoxicity. • Methionine deficiency exacerbated Dox-induced cardiotoxicity and cardiac dysfunction • Methionine deficiency aggravated deterioration of mitochondrial integrity and autophagy activity in Dox-induced cardiotoxicity • Methionine is essential in Dox-induced impairment of mitophagy • Appropriate methionine supplementation partially inhibited Dox-induced cardiotoxicity

Source: Free Radical Biology and Medicine

DOI: 10.1016/j.freeradbiomed.2025.02.044

Authors: Yijun Xin, Yong Zhang, Zhaoji Yuan, Siying Li

Institution: Shandong First Medical University

Language: English

Topic: Chemotherapy-induced cardiotoxicity and mitigation

Subfield: Cardiology and Cardiovascular Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,240