Drosophila TRIM32 cooperates with glycolytic enzymes to promote cell growth

• Published in: eLife 2020-03, Vol.9
• Main Authors: Bawa, Simranjot, Brooks, David S, Neville, Kathryn E, Tipping, Marla, Sagar, Md Abdul, Kollhoff, Joseph A, Chawla, Geetanjali, Geisbrecht, Brian V, Tennessen, Jason M, Eliceiri, Kevin W, Geisbrecht, Erika R
• Format: Article
• Language: English
• Subjects: Amino acids; Animals; BASIC BIOLOGICAL SCIENCES; Biomass; Biosynthesis; cancer; Cancer Biology; Carbohydrates; Cell Biology; Cell Cycle; Cell division; Cell growth; Cell Proliferation; Crystal structure; Dietary supplements; Drosophila; Drosophila melanogaster - enzymology; Drosophila melanogaster - genetics; Drosophila melanogaster - growth & development; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Enzymes; Glucose - metabolism; Glycolysis; Glycolysis - genetics; Homeostasis; Insects; Intermediates; Larva - growth & development; Metabolic pathways; Metabolism; muscle; Mutation; Oxidative metabolism; Peptides; Phosphoglycerate mutase; Physiology; Proteins; TRIM32; Tripartite Motif Proteins - genetics; Tripartite Motif Proteins - metabolism; Tumorigenesis; Ubiquitin-Protein Ligases - genetics; Ubiquitin-Protein Ligases - metabolism
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.52358

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 TRIM32, encoded by , 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 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.