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Research Article

Antifungal drug itraconazole targets VDAC1 to modulate the AMPK/mTOR signaling axis in endothelial cells

Sarah A. Head, Wei Shi, Liang Zhao, Kirill Gorshkov, Kalyan Pasunooti, Yue Chen, Zhiyou Deng, Ruo-jing Li, Joong Sup Shim, Wenzhi Tan, Thomas Hartung, Jin Zhang, Yingming Zhao, Marco Colombini, and Jun O. Liu
PNAS first published December 10, 2015; https://doi.org/10.1073/pnas.1512867112
Sarah A. Head
aDepartment of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205;
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Wei Shi
aDepartment of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205;
bDepartment of Chemistry and Biochemistry, University of Arkansas, Fayetteville, AR 72701;
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Liang Zhao
cDepartment of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205;
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Kirill Gorshkov
aDepartment of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205;
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Kalyan Pasunooti
aDepartment of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205;
dDivision of Structural Biology and Biochemistry, School of Biological Sciences, Nanyang Technological University, Singapore 637551;
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Yue Chen
eBen May Department of Cancer Research, The University of Chicago, Chicago, IL 60637;
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Zhiyou Deng
eBen May Department of Cancer Research, The University of Chicago, Chicago, IL 60637;
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Ruo-jing Li
aDepartment of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205;
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Joong Sup Shim
aDepartment of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205;
fFaculty of Health Sciences, University of Macau, Taipa, Macau Special Administrative Region, China;
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Wenzhi Tan
gDepartment of Biology, University of Maryland, College Park, MD 20742;
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Thomas Hartung
cDepartment of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205;
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Jin Zhang
aDepartment of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205;
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Yingming Zhao
eBen May Department of Cancer Research, The University of Chicago, Chicago, IL 60637;
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Marco Colombini
gDepartment of Biology, University of Maryland, College Park, MD 20742;
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Jun O. Liu
aDepartment of Pharmacology and Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205;
hDepartment of Oncology, Johns Hopkins School of Medicine, Baltimore, MD 21205
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  • For correspondence: joliu@jhu.edu
  1. Edited by Michael N. Hall, University of Basel, Basel, Switzerland, and approved November 12, 2015 (received for review July 7, 2015)

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    • Download Movie_S01 (MP4) - HUVEC expressing the AMPK-activity reporter ABKAR were treated with 2 µM itraconazole (*), followed by 20 mM 2DG (^). Pseudocolor represents the yellow/cyan emission ratio, as shown in Fig. 3D.
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Itraconazole targets VDAC1 to modulate AMPK/mTOR
Sarah A. Head, Wei Shi, Liang Zhao, Kirill Gorshkov, Kalyan Pasunooti, Yue Chen, Zhiyou Deng, Ruo-jing Li, Joong Sup Shim, Wenzhi Tan, Thomas Hartung, Jin Zhang, Yingming Zhao, Marco Colombini, Jun O. Liu
Proceedings of the National Academy of Sciences Dec 2015, 201512867; DOI: 10.1073/pnas.1512867112

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Itraconazole targets VDAC1 to modulate AMPK/mTOR
Sarah A. Head, Wei Shi, Liang Zhao, Kirill Gorshkov, Kalyan Pasunooti, Yue Chen, Zhiyou Deng, Ruo-jing Li, Joong Sup Shim, Wenzhi Tan, Thomas Hartung, Jin Zhang, Yingming Zhao, Marco Colombini, Jun O. Liu
Proceedings of the National Academy of Sciences Dec 2015, 201512867; DOI: 10.1073/pnas.1512867112
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