Language
English
Publication Date
9-17-2024
Journal
Molecular Pharmacology
DOI
10.1124/molpharm.124.000889
PMID
39168657
PMCID
PMC11413914
PubMedCentral® Posted Date
10-1-2024
PubMedCentral® Full Text Version
Post-print
Abstract
Autophagy is an essential self-degradative and recycling mechanism that maintains cellular homeostasis. Estrogen receptor-related orphan receptors (ERRs) are fundamental in regulating cardiac metabolism and function. Previously, we showed that ERR agonists improve cardiac function in models of heart failure and induce autophagy. Here, we characterized a mechanism by which ERRs induce the autophagy pathway in cardiomyocytes. Transcription factor EB (TFEB) is a master regulator of the autophagy-lysosome pathway and has been shown to be crucial regulator of genes that control autophagy. We discovered that TFEB is a direct ERR target gene whose expression is induced by ERR agonists. Activation of ERR results in increased TFEB expression in both neonatal rat ventricular myocytes and C2C12 myoblasts. An ERR-dependent increase in TFEB expression results in increased expression of an array of TFEB target genes, which are critical for the stimulation of autophagy. Pharmacologically targeting ERR is a promising potential method for the treatment of many diseases where stimulation of autophagy may be therapeutic, including heart failure.
Keywords
Animals, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Autophagy, Receptors, Estrogen, Rats, Mice, Myocytes, Cardiac, Humans, Cell Line, ERRalpha Estrogen-Related Receptor, Rats, Sprague-Dawley
Published Open-Access
yes
Recommended Citation
Losby, McKenna; Hayes, Matthew; Valfort, Aurore; et al., "The Estrogen Receptor-Related Orphan Receptors Regulate Autophagy through TFEB" (2024). Faculty, Staff and Students Publications. 6410.
https://digitalcommons.library.tmc.edu/baylor_docs/6410