HT29 and HCT116 colon cancer cell lines were treated with acetate and its effect on mitochondrial proliferation, reactive oxygen species, density, permeability transition pore, cellular bioenergetics, gene expression of acetyl-CoA synthetase 1 (ACSS1) and 2 (ACSS2), and lipid levels were investigated. Here, ACSS2 is linked to malignant colon neoplasm.