Alterations of intracellular pH homeostasis in apoptosis: origins and roles

Intracellular pH (pH(i)) has an important role in the maintenance of normal cell function, and hence this parameter has to be tightly controlled within a narrow range, largely through the activity of transporters located at the plasma membrane. These transporters can be modulated by endogenous or exogenous molecules as well as, in some pathological situations, leading to pH(i) changes that have been implicated in both cell proliferation and cell death. Whereas intracellular alkalinization seems to be a common feature of proliferative processes, the precise role of pH(i) in apoptosis is still unclear. The present review gathers the most recent advances along with previous data on both the origin and the role of pH(i) alterations in apoptosis and highlights the major concerns that merit further research in the future. Special attention is given to the possible role played by pH(i)-regulating transporters.