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Updated: Aug 5, 2026
08:09
A Doxorubicin-induced Cardiomyopathy Model in Adult Zebrafish
Published on: June 7, 2018
ATP Synthase Inhibitory Factor-1 Deficiency Attenuates Doxorubicin Cardiotoxicity by Preserving Mitochondrial
Parnia Mobasheran1,2, Ankit Aryal2, Jazmine Aguilar1,2
1Department of Pharmacology and Experimental Therapeutics, School of Graduate Studies, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
International Journal of Molecular Sciences
|July 28, 2026
Summary
Doxorubicin (DOX) causes heart damage by affecting mitochondria. ATP synthase inhibitory factor-1 (IF1) plays a key role in this process, with its inhibition potentially protecting the heart from DOX-induced cardiotoxicity.
Area of Science:
- Cardiology
- Biochemistry
- Molecular Biology
Background:
- Doxorubicin (DOX) is a vital chemotherapy drug, but its use is limited by cardiotoxicity.
- Mitochondrial dysfunction and altered metabolism are hallmarks of DOX-induced cardiac injury.
- ATP synthase inhibitory factor-1 (IF1) regulates mitochondrial ATP synthesis, but its role in chemotherapy-induced cardiotoxicity is unknown.
Purpose of the Study:
- To investigate the role of IF1 in doxorubicin-induced cardiotoxicity.
- To determine if modulating IF1 activity can protect against DOX-induced cardiac injury.
Main Methods:
- Utilized wild-type and IF1 knockout mice, isolated cardiac mitochondria, and cultured cardiomyocytes (neonatal and human AC16).
- Assessed cardiac function via echocardiography, mitochondrial function through respirometry and metabolic flux analysis.
- Evaluated myocardial injury using histological and ultrastructural analyses.
Main Results:
- DOX treatment increased cardiac IF1 protein levels.
- IF1 deficiency improved mitochondrial respiration and attenuated cardiac dysfunction and ultrastructural damage post-DOX.
- Overexpression of a dominant-negative IF1 mutant preserved metabolic activity and mitochondrial respiration in DOX-treated cardiomyocytes.
Conclusions:
- IF1 is a critical regulator of metabolic adaptation to DOX stress.
- Upregulated IF1 may support glycolysis during mitochondrial stress, while IF1 inhibition preserves mitochondrial function.
- Targeting IF1 presents a potential therapeutic strategy in cardio-oncology to mitigate DOX-induced cardiotoxicity.
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