Paraptosis

Paraptosis (from the Greek παρά para, "related to" and apoptosis) is a type of programmed cell death, morphologically distinct from apoptosis and necrosis. The defining features of paraptosis are cytoplasmic vacuolation, independent of caspase activation and inhibition, and lack of apoptotic morphology. Paraptosis lacks several of the hallmark characteristics of apoptosis, such as membrane blebbing, chromatin condensation, and nuclear fragmentation. Like apoptosis and other types of programmed cell death, the cell is involved in causing its own death, and gene expression is required. This is in contrast to necrosis, which is non-programmed cell death that results from injury to the cell.

Paraptosis has been found in some developmental and neurodegenerative cell deaths, as well as induced by several cancer drugs.

Paraptosis was not recognized as a form of cell death by the Nomenclature Committee on Cell Death in their 2018 review article. The use of this term was explicitly discouraged by the Committee in their 2012 revision

The first reported use of the term "paraptosis" was by Sabina Sperandio et al. in 2000. The group used human insulin-like growth factor 1 receptor (IGF-1R) to stimulate cell death in 293T cells and mouse embryonic fibroblasts, observing distinct differences from other forms of cell death. They coined the term "paraptosis", derived from the Greek preposition para, meaning beside or related to, and apoptosis.

While Sperandio was the first to publish the term paraptosis, this was not the first time cell death with the properties of paraptosis was observed. Terms such as "cytoplasmic" and "type 3 cell death" had previously been used to describe these forms of cell death. These forms are very similar to paraptosis morphologically, and it is possible that some instances of cell death originally described as one of these forms are occurrences of paraptosis.

Paraptosis is a form of type III programmed cell death with a unique combination of certain apoptotic and necrotic characteristics. Paraptosis does not demonstrate nuclear fragmentation, formation of apoptotic bodies, or definitive demonstration of chromatin condensation - all seen in apoptosis. Instead, paraptosis displays a somewhat primitive cell death path, comparable to necrosis, including characteristic cytoplasmic vacuole formation and late mitochondrial swelling and clumping. The number and size of vacuoles increases over time. Eventually, the vacuole sizes reach a point of no return and the cell cannot recover.

Similar to apoptosis, staining techniques can be used to identify paraptotic cells by highlighting the translocation of phosphatidylserine from the plasma membrane cytoplasmic (inner) leaflet to the cell surface or outer leaflet.

Paraptosis morphology changes are similar to the morphological changes undergone during the development of the nervous system.