has been shown to be caspase-3 independent. The primary determinant of cell death occurring via the oncotic or apoptotic pathway is cellular ATP levels. Apoptosis is contingent upon ATP levels to form the energy dependent apoptosome. A distinct biochemical event only seen in oncosis is the rapid depletion of intracellular ATP. The lack of intracellular ATP results in a deactivation of sodium and potassium ATPase within the compromised cell membrane. The lack of ion transport at the cell membrane leads to an accumulation of sodium and chloride ions within the cell with a concurrent water influx, contributing to the hallmark cellular swelling of oncosis. As with apoptosis, oncosis has been shown to be genetically programmed and dependent on expression levels of uncoupling protein-2 (UCP-2) in HeLa cells. An increase in UCP-2 levels leads to a rapid decrease in mitochondrial membrane potential, reducing mitochondrial NADH and intracellular ATP levels, initiating the oncotic pathway. The anti-apoptotic gene product Bcl-2 is not an active inhibitor of UCP-2 initiated cell death, further distinguishing oncosis and apoptosis as distinct cellular death mechanisms. References Biochemistry Cell biology Cell death