REPTOR and CREBRF Encode Key Regulators of Muscle Energy Metabolism

Overview

Journal Nat Commun

Specialty Biology

Date 2023 Aug 15

PMID 37582831

Authors

Pedro Saavedra

Phillip A Dumesic

Yanhui Hu

Elizabeth Filine

Patrick Jouandin

Richard Binari

Sarah E Wilensky

Jonathan Rodiger

Haiyun Wang

Weihang Chen

Ying Liu

Bruce M Spiegelman

Norbert Perrimon

Affiliations

Soon will be listed here.

Abstract

Metabolic flexibility of muscle tissue describes the adaptive capacity to use different energy substrates according to their availability. The disruption of this ability associates with metabolic disease. Here, using a Drosophila model of systemic metabolic dysfunction triggered by yorkie-induced gut tumors, we show that the transcription factor REPTOR is an important regulator of energy metabolism in muscles. We present evidence that REPTOR is activated in muscles of adult flies with gut yorkie-tumors, where it modulates glucose metabolism. Further, in vivo studies indicate that sustained activity of REPTOR is sufficient in wildtype muscles to repress glycolysis and increase tricarboxylic acid (TCA) cycle metabolites. Consistent with the fly studies, higher levels of CREBRF, the mammalian ortholog of REPTOR, reduce glycolysis in mouse myotubes while promoting oxidative metabolism. Altogether, our results define a conserved function for REPTOR and CREBRF as key regulators of muscle energy metabolism.

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