Cell volume in the regulation of metabolism, cell proliferation and apoptotic cell death

Alterations of cell volume trigger a large number of cell volume regulatory mechanisms including ion transport, osmolyte accumulation, metabolism and expression of appropriate genes. A wealth of cellular signaling pathways link cell volume to the respective regulatory mechanisms. In the past few years it has become apparent that alterations of cell volume and the subsequent activation of cell volume regulatory mechanisms participate as part of the signaling machinery in the regulation of a variety of cellular functions including metabolism, cell proliferation and apoptotic cell death. Cell swelling inhibits degradation and favours formation of macromolecules such as proteins and glycogen, effects reversed by cell shrinkage. It is discussed that insulin exerts its antiproteolytic effect simply by inducing cell swelling due to KCI uptake through activation of Na+,K+,2Cl(-) cotransport, Na+/H+ exchange and Na+/K+ ATPase. Glucagon triggers proteolysis by cell shrinkage due to activation of ion channels. Moreover, the case will be made that stimulation of cell proliferation by expression of Ras is paralleled by increase of cell volume due to activation of Na+,K+,2Cl(-) cotransport and Na+/H+ exchange and that CD95 induced cell death is paralleled by activation of cell volume regulatory Cl- channels. However, considerable additional experimentation is required to fully elucidate the role of cell volume in the control of metabolism, cell proliferation and cell death.