From Mutation to Metabolism: Environmental and Dietary Toxins as Upstream Drivers of Mitochondrial Dysfunction and Chronic Disease

Environmental and dietary exposures contribute to the modern burden of cancer, atherosclerotic cardiovascular disease (ASCVD), and type 2 diabetes mellitus (T2DM). While mutagenesis remains central to carcinogenesis, many exposures impair mitochondrial function—disrupting electron transport, depolarizing membranes, damaging mitochondrial DNA, and amplifying reactive oxygen species. These mitochondrial injuries converge on oxidative stress, chronic inflammation, endothelial dysfunction, and insulin resistance, thereby linking diverse hazards (industrial solvents, pesticides, heavy metals, air pollution) and dietary patterns (ultra-processed foods, high glycemic load) to common chronic diseases. This narrative review synthesizes human epidemiology with mechanistic evidence to map exposures → mitochondrial injury → disease end points, grading the strength of evidence and distinguishing hazard from risk. We highlight robust associations (e.g., benzene–leukemia, PM2.5–ASCVD, cadmium–CVD/T2DM) and areas of uncertainty (e.g., EMF, omega-6 oils). By centering mitochondria, we offer a unifying framework for prevention policy and clinical practice, and outline research priorities for exposomic measurement, mitochondrial biomarkers, and intervention trials.