Scholarlink

<p>Anthracyclines are cornerstone agents in oncology, yet their cardiotoxic effects may do more than inflict damage—they may uncover latent cardiac vulnerabilities. This mini-review examines anthracycline-induced mitochondrial stress as a potential diagnostic stressor that exposes subclinical impairments in cardiomyocyte energetics and quality control. We focus on receptor-mediated mitophagy, particularly the TRDMT1–BNIP3 epitranscriptomic axis, which enables organelle clearance independently of membrane depolarization, and the canonical PINK1–Parkin pathway, highlighting their distinct and sometimes context-dependent roles. Unlike the canonical PINK1–Parkin pathway, which is typically activated by mitochondrial depolarization, the TRDMT1-BNIP3 axis may better reflect early adaptive responses to specific cellular stresses. We summarize emerging evidence from iPSC-derived cardiomyocytes, animal models, and molecular imaging studies, suggesting that mitochondrial dysfunction precedes overt systolic decline. We propose that doxorubicin-induced effects on mitophagy pathways may serve as a functional indicator of mitochondrial reserve, providing a basis for risk stratification and targeted cardioprotection. Reframing cardiotoxicity as a measurable biological signal—not only as injury—could improve early detection of heart failure susceptibility by revealing these hidden vulnerabilities. These insights are hypothesis-generating and require further clinical validation before implementation in diagnostic frameworks.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Anthracyclines as diagnostic stressors: mitophagy signaling and hidden cardiac vulnerability

  • 期刊论文

  • 发表日期：

    2025年7月11日

查看全文
  • Natalia Kulicka,
  • Artur Dziewierz

摘要

Anthracyclines are cornerstone agents in oncology, yet their cardiotoxic effects may do more than inflict damage—they may uncover latent cardiac vulnerabilities. This mini-review examines anthracycline-induced mitochondrial stress as a potential diagnostic stressor that exposes subclinical impairments in cardiomyocyte energetics and quality control. We focus on receptor-mediated mitophagy, particularly the TRDMT1–BNIP3 epitranscriptomic axis, which enables organelle clearance independently of membrane depolarization, and the canonical PINK1–Parkin pathway, highlighting their distinct and sometimes context-dependent roles. Unlike the canonical PINK1–Parkin pathway, which is typically activated by mitochondrial depolarization, the TRDMT1-BNIP3 axis may better reflect early adaptive responses to specific cellular stresses. We summarize emerging evidence from iPSC-derived cardiomyocytes, animal models, and molecular imaging studies, suggesting that mitochondrial dysfunction precedes overt systolic decline. We propose that doxorubicin-induced effects on mitophagy pathways may serve as a functional indicator of mitochondrial reserve, providing a basis for risk stratification and targeted cardioprotection. Reframing cardiotoxicity as a measurable biological signal—not only as injury—could improve early detection of heart failure susceptibility by revealing these hidden vulnerabilities. These insights are hypothesis-generating and require further clinical validation before implementation in diagnostic frameworks.