Ions, cell volume, and apoptosis

Programmed cell death culminating in apoptosis is responsible for normal tissue homeostasis and has increasingly been implicated in mediating pathological cell loss (1–3). Apoptosis is accompanied by characteristic morphological changes, including cell body and nuclear condensation, chromatin margination, and the formation of membrane-bound remnants (apoptotic bodies) (4). In recent years much has been learned about the molecular underpinnings of apoptosis, including the release of cytochrome c from mitochondria, modulation by bcl-2 and related genes, and a central role for caspase activation in triggering final events (5). However, despite the universal prominence of cell volume loss in cells undergoing apoptosis, the relationship between this event and ensuing cell death remains uncertain. As posed by Bortner and Cidlowski (6), a key question is whether cell volume loss is “a passive, secondary feature of the cell death process” or a driver of the process.