To further characterize mechanisms involved in the regulation of glycolysis by TRAP1, this study addresses the mechanisms of TRAP1 regulation of glycolytic pathway, showing for the first time a new interaction between TRAP1 and the most relevant glycolytic enzyme PFK1 and the relationship between TRAP1 glycolytic regulation and its control of mitochondrial respiration in colorectal carcinoma cells (CRCs). Here, TRAP1 is linked to colorectal carcinoma.