Year: 2023
Type: article
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.
Source: Nature Communications
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,290
Funders: Howard Hughes Medical Institute, U.S. Department of Health and Human Services, Damon Runyon Cancer Research Foundation, Beth Israel Deaconess Medical Center, Cancer Research UK, Human Frontier Science Program, National Institutes of Health, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Arthritis and Musculoskeletal and Skin Diseases
Awards: G1904072893, G2654233361, G320121671, G3401437241, Cellular and Biochemical Pathways of Adipose Metabolism and Thermogenesis, Identification of Presinilin downstream targets in neuronal survival, G4495182536, G4751926760, CANCAN ? CORNELL, G6178546669, Characterization of the Insulin to Autophagy Pathway in Muscles, G6592930706, G669404050, G6962561824, G8057264522, G8885387502, G89895783, Molecular Pathogenesis of the Hamartoma Syndromes, PGC1alpha Pathway: Novel Intracellular and Extracellular Mediators
OpenAlex ID: W4385840143