Apoptosis: controlled demolition at the cellular level
Rebecca C. Taylor, Sean P. Cullen and Seamus J. Martin
Abstract | Apoptosis is characterized by a series of dramatic perturbations to the cellular architecture that contribute not only to cell death, but also prepare cells for removal by phagocytes and prevent unwanted immune responses. Much of what happens during thedemolition phase of apoptosis is orchestrated by members of the caspase family of cysteine proteases. These proteases target several hundred proteins for restricted proteolysis in a controlled manner that minimizes damage and disruption to neighbouring cells and avoids the release of immunostimulatory molecules.
A cell that can engulf and ingest foreign material, such as an apoptotic cell corpse, which then undergoes digestion within lysosomes.
One of a family of proteases that have an essential Cys residue in their active site and a requirement for an Asp residue in the substrate cleavage site. Initiator caspases are typically activated in response to particular stimuli, whereas effector caspases are particularly important for the ordered dismantling of vital cellular structures.
During apoptosis, cells collapse into small intact fragments that exclude vital dyes. Such fragments are termed apoptotic bodies.
Apoptosis is a mode of cell death that is used by multi cellular organisms to dispose of unwanted cells in a diver sity of settings1,2. In many ways, what happens during apoptosis is akin to how large buildings aredemolished to make way for new developments. During demolition, it is important that the process is carried out in a safe and controlled manner to ensure that neighbouring structures remain unaffected. To achieve this, a special ized demolition squad is called in and, all being well, these experts carry out the task in a precise and highly efficient manner. After demolition has been completed, the debrisis removed and a new structure takes the place of the old one within a short time. Similar to the scenario outlined above, cells that undergo apoptosis are also dismantled from within, in a controlled manner that minimizes damage and disrup tion to neighbouring cells1. The resulting cellular debris is then removed, typically by professional phagocytes1, and a new cell typically takes the placeof the old one in a matter of hours. Here, we focus on the events that take place during the demolition phase of apoptosis that result in the controlled dismantling of a range of key structures within the cell and its subsequent dis posal. These events are orchestrated primarily, but not exclusively, by members of a family of cysteine proteases known as caspases3,4.
Molecular Cell BiologyLaboratory, Department of Genetics, The Smurfit Institute, Trinity College, Dublin 2, Ireland. Correspondence to S.J.M. e-mail: email@example.com doi:10.1038/nrm2312 Published online 12 December 2007
Cellular demolition: a broad perspective So what actually happens during apoptosis? From the outside, it appears that cells that undergo this form of cell death initially become rounded and retract fromneighbouring cells, which is reminiscent of what also happens when cells undergo mitosis (FIG. 1a) . This is accompanied, or followed closely, by a prolonged period of dynamic plasma membrane blebbing, which
frequently culminates in the ‘pinching off ’ of many of these blebs as small vesicles that have been named apoptotic bodies (FIG. 1a; Supplementary information S1 (movie)). For reasonsthat will be discussed below, cells that undergo apoptosis are readily recognized as being dif ferent from their viable counterparts and are rapidly engulfed by phagocytes for recycling of their con tents1,2,5. This event is particularly remarkable when it is considered that phagocytes are normally engaged in the business of recognizing and removing foreign, or ‘nonself ’, entities. However,...