Laboratory for Optical and Computational Instrumentation, Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, United States
Joseph A Kollhoff
Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, United States
Geetanjali Chawla
Regional Centre for Biotechnology, NCR Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon Expressway, Faridabad, India; Department of Biology, Indiana University, Bloomington, United States
Brian V Geisbrecht
Department of Biochemistry and Molecular Biophysics, Kansas State University, Manhattan, United States
Laboratory for Optical and Computational Instrumentation, Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, United States
Cell growth and/or proliferation may require the reprogramming of metabolic pathways, whereby a switch from oxidative to glycolytic metabolism diverts glycolytic intermediates towards anabolic pathways. Herein, we identify a novel role for TRIM32 in the maintenance of glycolytic flux mediated by biochemical interactions with the glycolytic enzymes Aldolase and Phosphoglycerate mutase. Loss of Drosophila TRIM32, encoded by thin (tn), shows reduced levels of glycolytic intermediates and amino acids. This altered metabolic profile correlates with a reduction in the size of glycolytic larval muscle and brain tissue. Consistent with a role for metabolic intermediates in glycolysis-driven biomass production, dietary amino acid supplementation in tn mutants improves muscle mass. Remarkably, TRIM32 is also required for ectopic growth - loss of TRIM32 in a wing disc-associated tumor model reduces glycolytic metabolism and restricts growth. Overall, our results reveal a novel role for TRIM32 for controlling glycolysis in the context of both normal development and tumor growth.
