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https://open.uns.ac.rs/handle/123456789/14149
Title: | 3,4-Dimethoxychalcone induces autophagy through activation of the transcription factors TFE3 and TFEB | Authors: | Chen G. Xie W. Nah J. Sauvat A. Liu P. Pietrocola F. Sica V. Carmona-Gutierrez D. Zimmermann A. Pendl T. Tadic J. Bergmann M. Hofer S. Domuz, Lana Lachkar S. Markaki M. Tavernarakis N. Sadoshima J. Madeo F. Kepp O. Kroemer G. |
Issue Date: | 7-Nov-2019 | Journal: | EMBO Molecular Medicine | Abstract: | © 2019 The Authors. Published under the terms of the CC BY 4.0 license Caloric restriction mimetics (CRMs) are natural or synthetic compounds that mimic the health-promoting and longevity-extending effects of caloric restriction. CRMs provoke the deacetylation of cellular proteins coupled to an increase in autophagic flux in the absence of toxicity. Here, we report the identification of a novel candidate CRM, namely 3,4-dimethoxychalcone (3,4-DC), among a library of polyphenols. When added to several different human cell lines, 3,4-DC induced the deacetylation of cytoplasmic proteins and stimulated autophagic flux. At difference with other well-characterized CRMs, 3,4-DC, however, required transcription factor EB (TFEB)- and E3 (TFE3)-dependent gene transcription and mRNA translation to trigger autophagy. 3,4-DC stimulated the translocation of TFEB and TFE3 into nuclei both in vitro and in vivo, in hepatocytes and cardiomyocytes. 3,4-DC induced autophagy in vitro and in mouse organs, mediated autophagy-dependent cardioprotective effects, and improved the efficacy of anticancer chemotherapy in vivo. Altogether, our results suggest that 3,4-DC is a novel CRM with a previously unrecognized mode of action. | URI: | https://open.uns.ac.rs/handle/123456789/14149 | ISSN: | 17574676 | DOI: | 10.15252/emmm.201910469 |
Appears in Collections: | PMF Publikacije/Publications |
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