A Reverse-Osmosis Model of Apoptotic Shrinkage

• Published in: Frontiers in cell and developmental biology Vol. 8; p. 588721
• Main Authors: Rana, Priyanka S., Model, Michael A.
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 23.10.2020
• Subjects: apoptotic volume decrease; Cell and Developmental Biology; cytoskeletal contraction; cytoskeleton; intracellular pressure; osmolytes; potassium channels
• ISSN: 2296-634X; 2296-634X
• DOI: 10.3389/fcell.2020.588721

The standard theory of apoptotic volume decrease (AVD) posits activation of potassium and/or chloride channels, causing an efflux of ions and osmotic loss of water. However, in view of the multitude of possible channels that are known to support apoptosis, a model based on specific signaling to a channel presents certain problems. We propose another mechanism of apoptotic dehydration based on cytoskeletal compression. As is well known, cytoskeleton is not strong enough to expel a substantial amount of water against an osmotic gradient. It is possible, however, that an increase in intracellular pressure may cause an initial small efflux of water, and that will create a small concentration gradient of ions, favoring their exit. If the channels are open, some ions will exit the cell, relieving the osmotic gradient; in this way, the process will be able to continue. Calculations confirm the possibility of such a mechanism. An increase in membrane permeability for water or ions may also result in dehydration if accompanied even by a constant cytoskeletal pressure. We review the molecular processes that may lead to apoptotic dehydration in the context of this model.