Targeting the Mitochondria to Enhance Tumor Suppression

A continuous supply of biochemical energy is required in order for cells to perform their physiologic functions as well as maintain their own homeostasis. Cellular energy is determined largely by the ratio of intracellular ATP to ADP. A high ratio of ATP/ADP is produced primarily by the oxidation of glucose. This process can be divided into two major steps. The first, which takes place in the cytosol, is glycolysis, which produces 2 mol of ATP per 1 mol of glucose utilized. The end product of glycolysis, pyruvate, is either converted to lactate and expelled from the cells or is utilized by the second step, which takes place in the mitochondria, and includes the citric acid cycle and oxidative phosphorylation (OXPHOS). Further oxidation of pyruvate in the mitochondria leads to the production of reducing equivalents (NADH and FADH₂ ). Under aerobic conditions these compounds fuel OXPHOS, producing between 29 and 36 mol of ATP per 1 mol of glucose in addition to the 2 mol produced by glycolysis alone. An average adult converts 50–75 kg of ADP into ATP per day, which is used mainly to regulate the homeostasis of cells (mostly by regulating Na⁺ /K⁺ channels) and to enable motion (muscle contraction) and anabolic reactions (mostly macromolcule synthesis). The latter is important for promoting cell growth and proliferation, as cells must synthesize proteins, DNA, and other macromolcule in order to divide (1 ).