Mitochondria combine hydrogen derived from dietary carbohydrates and fats with oxygen to generate heat and ATP. Electrons flowing through the electron transport chain, made up of OXPHOS complexes I through V, are used to pump protons out of the mitochondrial inner membrane. This creates an electrical charge used to generate ATP, which powers most of the cell’s biochemical reactions. As a toxic by-product of OXPHOS, mitochondria generate reactive oxygen species (ROS), called free radicals. At high levels, free radicals damage mtDNA, nuclear DNA, proteins, lipids, and other molecules in the cell. As the percentage of mutated mtDNA in a cell increases, mitochondrial energy output declines, ROS production increases, and the likelihood of cell death increases. Through the work of Wallace and others, energy deficiency caused by these factors, as well as inherited mtDNA mutations, have been linked to numerous diseases.