Mitochondrial determinants of doxorubicin- induced cardiomyopathy

Kendall B. Wallace, Vilma A. Sardão, Paulo J. Oliveira

Research output: Contribution to journalReview article

1 Scopus citations

Abstract

Anthracycline-based chemotherapy can result in the development of a cumulative and progressively developing cardiomyopathy. Doxorubicin is one of the most highly prescribed anthracyclines in the United States due to its broad spectrum of therapeutic efficacy. Interference with different mitochondrial processes is chief among the molecular and cellular determinants of doxorubicin cardiotoxicity, contributing to the development of cardiomyopathy. The present review provides the basis for the involvement of mitochondrial toxicity in the different functional hallmarks of anthracycline toxicity. Our objective is to understand the molecular determinants of a progressive deterioration of functional integrity of mitochondria that establishes a historic record of past drug treatments (mitochondrial memory) and renders the cancer patient susceptible to subsequent regimens of drug therapy. We focus on the involvement of doxorubicin-induced mitochondrial oxidative stress, disruption of mitochondrial oxidative phosphorylation, and permeability transition, contributing to altered metabolic and redox circuits in cardiac cells, ultimately culminating in disturbances of autophagy/mitophagy fluxes and increased apoptosis. We also suggest some possible pharmacological and nonpharmacological interventions that can reduce mitochondrial damage. Understanding the key role of mitochondria in doxorubicin-induced cardiomyopathy is essential to reduce the barriers that so dramatically limit the clinical success of this essential anticancer chemotherapy.

Original languageEnglish (US)
Pages (from-to)926-941
Number of pages16
JournalCirculation research
DOIs
StateAccepted/In press - Jan 1 2020

Keywords

  • Cardiomyopathy
  • Cardiotoxicity
  • Doxorubicin
  • Mitochondria
  • Oxidative stress

PubMed: MeSH publication types

  • Journal Article

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