CREBBP and cancer: In cancer (including CRC), these mechanistic axes predict that CBP/p300 inhibition will reduce mitobiogenesis and sensitize OXPHOS-addicted tumors, PRMT inhibition may shift metabolic flux and affect mitochondrial enzyme activity, and EZH2 inhibition can rewire mitochondrial gene expression and ER–mitochondrial homeostasis, each producing distinct changes in mtDNA copy number, oxygen consumption rate (OCR), mitochondrial membrane potential, and mtROS (123, 283–285).