Drosophila TRIM32 cooperates with glycolytic enzymes to promote cell growth

Abstract

Control of tissue and organismal size requires the continual reprogramming of metabolic pathways to integrate biosynthetic and degradative signals. During cell growth and/or proliferation, one such mechanism that promotes the accumulation of cellular material is a switch from oxidative to glycolytic metabolism, whereby glycolytic intermediates are diverted towards anabolic pathways. How this switch is regulated in different tissues is not clear. Herein we identify a novel role for the tripartite motif (TRIM) family member, TRIM32, in the maintenance of glycolytic flux. Using a proteomics approach, we uncovered the glycolytic enzymes Aldolase (Ald) and Phosphoglycerate mutase 78 (Pglym) as TRIM32 interacting proteins. Loss of Drosophila TRIM32, encoded by the thin (tn) gene, showed a reduction in glycolytic activity and amino acid abundance. This altered metabolic profile caused a striking reduction in the overall size of two inherently glycolytic larval tissues – somatic muscles and the developing brain. Consistent with a role for metabolic intermediates in glycolysis‐driven biomass production, nutritional supplementation of amino acids in tn mutants restored muscle mass. Many tumors favor glycolytic metabolism to maximize substrate production for uncontrolled cell growth and proliferation. Remarkably, wing disc‐associated tumor growth is abolished upon loss of TRIM32. Our results reveal a novel connection between TRIM32 and the maintenance of glycolytic enzyme levels and upregulated pathway activity for the sustained growth of normal and cancerous tissue growth.Support or Funding InformationThis work was supported by a grant through the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) to E.R.G (R01AR060788). J.M.T. is supported by a MIRA award from NIGMS (R35GM119557).