What is Apoptosis and Programmed Cell Death?
Programmed cell death is the process in which healthy and normal cells activate an intracellular death program to ultimately commit suicide. Both plants and animals share a very similar pathway in which it is commonly seen that the nucleus condenses, the DNA fragments, condensing of the cytoplasm and plasma membrane shrinkage. Bcl-2 like proteins are conserved between both plants and animal systems of programmed cell death [4]. In plants, mitochondria have a role in programmed cell death just like in animals but it is also seen that the chloroplast are also involved. Accelerated Death Genes (ADG1 and ACD2) are seen in plants and not animals, code for enzymes that degrade the chlorophyll in chloroplasts, chloroplasts are also the site where many reactive oxygen species are produced (and these are involved in many programmed cell death pathways. When the plant is attacked by some sort of pathogen ACD2 is seen to actually localize between the chloroplast and mitochondria in order to intercept chloroplast derived ACD2 substrate molecules that would target the mitochondria and cause death The Staygreeb locus gene codes for a protein which functions in early degradation of chlorophyll via the disruption of light harvesting complexes ultimately putting a stop to photosynthesis in the cells undergoing cell death [3].

Mechanisms of Apoptosis
In animals the main process that is underwent in apoptosis; plants and unicellular organisms also go through such processes as properly regulated cell death is necessary for the survival of the organism Apoptosis has two main pathways in which it can begin, those are the intrinsic and extrinsic pathways. Biochemical recognition of the process is well understood as apoptosis has signature traits: detectable fragments of DNA cleaved into distinct sizes, flipping of membrane bound cells resulting of exposure of negatively charged phospholipids, a loss of electricac potential across inner membrane of mitochondria and the presence of Cytochrome C and its relocation from the mitochondria to the cytosol. Apoptosis is dependent on a intracellular proteolytic cascade which is mediated by caspsases. This cascade begins with a initiator procaspase which cleave and activate downstream executioner proteins. Executioner procaspases then travel further downstream and activate other executioners as well as target proteins. It is triggered by the assembling of initiator procaspases into an activation complex with the aid of adaptor proteins. It is the caspase recruitment domain (CARD) that allows the initiator procaspases to assemble in this way. Initiators cleave one another to activate each other, this spreads the signal of apoptosis as more and more initiators are activated [1].
The extrinsic pathway involves the binding of extracellular signal proteins to cell-surface death receptors. These receptors contain extracellular ligand-binding domain, a single transmembrane domain and an intracellular death domain which is required to Apoptosis. Adaptor proteins recruit initiators and form death inducing signaling processes known as DISC, which then signals downstream executioners to induce apoptosis [1].
The intrinsic pathway is dependent on the release of mitochondrial proteins into the cytosol. These proteins activate a caspase proteolytic cascade in the cytoplasm that leads to apoptosis. Cytochrome C is the crucial protein; in the mitochondria it binds to a procaspase which activates adaptor proteins that in turn causes it to form an apoptosome. Apoptosomes then recruit initiator procaspase-9 proteins and activate them. These proteins upon activation then activate downstream executioners to begin apoptosis [1].
Apoptosis is regulated by BCl2 proteins (these regulate the intrinsic pathways of apoptosis). BCl2 controls the release of cytochrome C. There are both anti-apoptotic and pro-apoptotic BCl2 proteins. Upon reception of stimuli, pro-apoptotic activate and aggregate which induces the release of cytochrome C into the Cytosol. BH3-only proteins are produced or activated in response to reception of apoptotic stimuli. They are the crucial link between the stimuli and the activation of the intrinsic pathway of apoptosis. Different stimuli activate different BH3-oly proteins. Inhibitors of apoptosis (IAP’s) prevent cells from committing suicide. Survival factors are a good example; these factors are extracellular signals that inhibit apoptosis and tell the cell to survive. Many animal cells require constant signaling for survival and these signals are secreted by target cells in the surrounding area. Factors they secrete bind to surface cell receptors and inhibit apoptosis. Upon a lack of signal reception the cell will begin to undergo apoptosis [1].

Why is Programmed Cell Death Important?
It is utilized in the elimination of cells that are no longer needed, elimination of entire structures that are no longer needed, regulation of cell numbers and size, and finally it acts as quality control in the removal of abnormal, nonfunctional, misplaced, or potentially dangerous cells within the organism. Regulated programmed cell death is essential to healthy functioning of the organism as a whole. In humans it is involved in the formation from the spade like structure to a hand and the formation of toes. Up to a point in utero humans have a tail as well, in which apoptosis removes because there is no need for that structure. Some diseases that deregulate this process can be extremely problematic and by understanding the genes and factors that control for it, then it is possible to understand how the disease alters it and treatments can thus be produced [1].

Cancer is a Disease Associated with Programmed Cell Death
Cancer is a very serious disease that involves the abnormal alteration in the function of apoptosis. In 50% of human cancer cases the p53 gene (which is responsible for production of p53 tumor suppression proteins) is mutated and nonfunctional meaning that it no longer promotes apoptosis and no longer performs cell cycle arrests in response to DNA damage. This enables cancerous cells to survive and proliferate. The longer these cells are alive the more time they have to allow mutations to accumulate which increases the chances of the cancerous cells becoming malignant.

Key Individuals
Programmed cell death was first described around the 1800’s, however it was the distinguishing between necrosis and apoptosis that really allowed research for apoptosis to take off. John Foxton Kerr was the individual who made this discovery. It was originally proposed to be called cell necrosis; however that was changed to apoptosis. John E. Sulston, Sydney Brenner, and Robert Horvitz are other important figure for their discovery of the genes that controlled apoptosis through their study of C. elegans, as they also discovered that these same genes function in humans for apoptosis [2].

Current Research
Developmentally programmed cell death in drosophila shows that apoptosis is required for the normal development of Drosophila through compiling research done on multiple aspects of Drosophila development, autophagy is also extremely important though it is not understood as well as apoptosis. Autophagy is often induced during periods of stress that could lead to cell death and could perhaps act as a regulated cell death mechanism [4]. An autophagic marker present on a cell going through cell death does not always mean that it is undergoing autophagy. Research concerning the manipulation of autophagy shows that there it has a specific role in certain scenarios. It can be utilized as a protective mechanism against oxidative stress [5]. The JNK pathway regulates expression of autophagy related genes and is seen in stress resistant phenotype of flies. Further insight into this pathway could help give insight into other mechanisms of programmed cell death and how they function, and with further studies correlating to autophagic methods of programmed cell death could provide us with information on defensive responses in correlation with certain stimuli (and to see its regulated role in the organism).
In Drosophila, apoptosis is an important mechanism that regulates specific cell death that is crucial during their development. It can be seen taking place in early embryogenesis and during the larval stages in which it can be seen in many tissues (especially the central nervous system). It is utilized in the differentiation of the adult eye during pupil development and during the larval-pupal transition. During this transition many of the larval tissues are destroyed; this is caused by the hormone ecdysone. Some of the components of their undergoing of programmed cell death differ than what was exposed through research done on C. elegans (the discovery of the genes regulating apoptosis was through C.elegans genome) and what is also seen in mammals; Bcl-2homologues are not essential for programmed cell death to take place in Drosophila. There was also a revealing of nonapoptotic cell deaths during development, caspases are not the main contributing factor. Eiger induced cell death leads to the c-Jun NH(2)-terminal kinase dependent production of reactive oxygen species. This pathway involves activation of tumor necrosis receptors, in which the Drosophila express Eiger (factor) and Wengen (receptor). Suppression of factors seen to regulate apoptosis in mammals (caspases) only leads to the slowing down of cell death as opposed to the complete stop of it. This mechanism is not completely understood, the role of the caspases in Drosophila are currently unknown. Further study of the genetics behind the mechanisms could expand knowledge on the development of species as they transition through important developmental stages as programmed cell death mechanisms and regulation may differ from species to species. [6].
Autophagy is linked to many functions in human cells including stress response, protein degredation, organelle turnover tumor suppression and caspase-independent cell death. Deregulation of autophagy is often associated with malignant tumor formation. The p53 gene can induce autophagy after stress through transcriptionally-dependent and independent mechanisms. Further research expanded on transcriptionally-dependent mechanisms by characterizing a p53 family target gene. This gene is known as ISG20L1[7]. This gene can be regulated by all 3 p53 family members. Expression of this gene in cancer cells led to decreased clonogenic survival and also through a gene knockout these researchers found that removing the expression of this gene decreases autophagic vacuoles. Further studies into this can lead to new cancer therapies in which perhaps fixing the misregulation of this gene in cancer cells could help to prevent mitosis from occurring.

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