Cited by 36Cardiac Ischemia and ReperfusionAutophagy in Disease and TherapyMitochondrial Function and Pathology

The cardioprotective compound cloxyquin uncouples mitochondria and induces autophagy

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Zhang, Jimmy, Nadtochiy, Sergiy M., Urciuoli, William R., Brookes, Paul S.·2016·American Journal of Physiology-Heart and Circulatory Physiology

Abstract

Mitochondrial quality control mechanisms have been implicated in protection against cardiac ischemia-reperfusion (IR) injury. Previously, cloxyquin (5-chloroquinolin-8-ol) was identified via phenotypic screening as a cardioprotective compound. Herein, cloxyquin was identified as a mitochondrial uncoupler in both isolated heart mitochondria and adult cardiomyocytes. Additionally, cardiomyocytes isolated from transgenic mice expressing green fluorescent protein-tagged microtubule-associated protein light chain 3 showed increased autophagosome formation with cloxyquin treatment. The autophagy inhibitor chloroquine abolished cloxyquin-induced cardioprotection in both cellular and perfused heart (Langendorff) models of IR injury. Finally, in an in vivo murine left anterior descending coronary artery occlusion model of IR injury, cloxyquin significantly reduced infarct size from 31.4 ± 3.4% to 16.1 ± 2.2%. In conclusion, the cardioprotective compound cloxyquin simultaneously uncoupled mitochondria and induced autophagy. Importantly, autophagy appears to be required for cloxyquin-induced cardioprotection.

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Crossref · 10.1152/ajpheart.00926.2014

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Authors
Zhang, J., Nadtochiy, S. M., Urciuoli, W. R., & Brookes, P. S.
Affiliations
University of Rochester Medicine (US)
Corresponding author
Brookes, Paul S.
Venue
American Journal of Physiology-Heart and Circulatory Physiology
Published
2016-01-01
Volume
310
Issue
1
Pages
H29-H38
ISSN
  • 0363-6135 (ISSN-L)
  • 1522-1539
OpenAlex
W2269587458
Cited by
36
References
50
Citations by year
2026: 4 · 2025: 1 · 2024: 2 · 2023: 4 · 2022: 5 · 2021: 2 · 2020: 3 · 2019: 5 · 2018: 1 · 2017: 5 · 2016: 4
FWCI
2.65
Type
journal article
Language
en
Open access
Locations
  • American Journal of Physiology-Heart and Circulatory Physiology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
HHS | National Institutes of Health (NIH) (R01 HL-071158, T32GM007356)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Keywords
mitochondrial uncoupling, autophagy, cardioprotection, myocardial ischemia-reperfusion injury, chloroquine, cardiomyocytes, mitochondrial quality control, infarct size, coronary artery occlusion, LC3
MeSH terms
Isolated Heart Preparation, Animals, Autophagy, Chloroquine, Chloroquinolinols, Dose-Response Relationship, Drug, Male, Mice, Inbred C57BL, Mice, Transgenic, Microtubule-Associated Proteins, Mitochondria, Heart, Myocardial Infarction, Recombinant Fusion Proteins, Time Factors, Uncoupling Agents, Myocardial Reperfusion Injury, Protective Agents, Myocytes, Cardiac, Green Fluorescent Proteins

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