Related Experiment Video

Updated: May 24, 2025

A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo
05:14

A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo

Published on: May 16, 2020

4.4K

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

Yijun Xin1, Yong Zhang1, Zhaoji Yuan2

  • 1Metabolism and Disease Research Center, Central Hospital Affiliated to Shandong First Medical University, Jinan, 250013, Shandong, China.

Free Radical Biology & Medicine
|March 3, 2025
PubMed

Insights

Methionine (Met) deficiency worsens doxorubicin (Dox)-induced heart damage by impairing mitophagy. Supplementing Met protects against Dox cardiotoxicity through the methionine-GCN2 pathway, offering a potential therapeutic strategy.

Area of Science:

  • Biochemistry
  • Cardiology
  • Molecular Biology

Background:

  • Doxorubicin (Dox) is a vital chemotherapy agent, but its clinical utility is limited by dose-dependent cardiotoxicity.
  • Impaired mitophagy, the selective degradation of damaged mitochondria, is a key mechanism in Dox-induced cardiomyopathy.

Purpose of the Study:

  • To investigate the role of methionine (Met) in regulating mitophagy within the context of Dox-induced cardiotoxicity.
  • To elucidate the molecular mechanisms by which Met influences Dox cardiotoxicity.

Main Methods:

  • Investigated the effects of Met deficiency and supplementation on Dox-treated models.
  • Analyzed oxidative stress markers, mitochondrial integrity, and autophagy pathways.
  • Examined the involvement of the general control nonderepressible 2 (GCN2) pathway.

Main Results:

  • Met deficiency exacerbated Dox-induced cardiotoxicity, increasing oxidative stress, mitochondrial damage, and disrupting autophagy.
  • Met supplementation alleviated Dox cardiotoxicity, mitigating cardiomyocyte damage and heart failure progression.
  • The protective effects of Met were mediated through the GCN2 signaling pathway.

Conclusions:

  • Methionine metabolism plays a critical role in mitigating Doxorubicin-induced cardiotoxicity.
  • The Met-GCN2 axis represents a promising therapeutic target for preventing or treating Dox-induced heart damage.
Keywords:
CardiotoxicityDoxorubicinMethionineMitophagy

More Related Videos

A Doxorubicin-induced Cardiomyopathy Model in Adult Zebrafish08:09

A Doxorubicin-induced Cardiomyopathy Model in Adult Zebrafish

Published on: June 7, 2018

9.7K
Protection of H9c2 Myocardial Cells from Oxidative Stress by Crocetin via PINK1/Parkin Pathway-Mediated Mitophagy07:40

Protection of H9c2 Myocardial Cells from Oxidative Stress by Crocetin via PINK1/Parkin Pathway-Mediated Mitophagy

Published on: May 26, 2023

1.0K

Related Concept Videos

Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
10.1K
Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
3.0K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.7K
The Electron Transport Chain01:30

The Electron Transport Chain

The electron transport chain or oxidative phosphorylation is an exothermic process in which free energy released during electron transfer reactions is coupled to ATP synthesis. This process is a significant source of energy in aerobic cells, and therefore inhibitors of the electron transport chain can be detrimental to the cell's metabolic processes.
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q...
15.9K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.4K