Mechanistic paradigms of cell death - revisited

Current Molecular Biology Reports

One of the vital aspects of a cell is cell death to continue their normal cell turnover, propagation, proper development, and the maintenance of the immune system. Cell death is an essential process in the body as it promotes the removal of unwanted cells. It is the programmed culling of cells in entire eukaryotic development processes to survive and progress for the next generation. Molecular aberration in the process of apoptosis may have pathological manifestations, including cancer, neurodegenerative disorders, autoimmune disease, and ischemic damage. Classically, cell death is categorized primarily into four different types: apoptosis, autophagy, necrosis, and entosis; depending on cellular and molecular signatures governing the pathway involved. The purpose of this review is to compare and contrast the recent literature on cell death and to familiarize with the current state of knowledge on this topic. In summary, the hallmarks of various modes of cell death are thoroughly explained along with the other types of cell death such as ferroptosis, pyroptosis, necroptosis, and lysosomal-dependent cell death.

… journal of oncology, 2002

Cell death and the subsequent post-mortem changes, called necrosis, are integral parts of normal development and maturation cycle. Despite the importance of this process, the mechanisms underlying cell death are still poorly understood. In the recent literature, cell death is said to occur by two alternative, opposite modes: apoptosis, a programmed, managed form of cell death, and necrosis, an unordered and accidental form of cellular dying. The incorrect consequence is the overlapping of: a) the process whereby cells die, cell death; and b) the changes that the cells and tissues undergo after the cells die. Only the latter process can be referred to as necrosis and represents a 'no return' process in cell life. In this review, we discuss the excellent basic research developed in this field during last decades and problems that remain to be resolved in defining both experimentally and mechanicistically the events that lead to and characterize cell death. inflammation and disturbed blood supply (1,2). Cell death is an important variable in cancer development, cancer prevention and cancer therapy (3-5). In the treatment of cancer, the major approach is the removal, by surgery, of the neoplasm and/or the induction of cell death in neoplastic cells by radiation, toxic chemicals, antibodies and/or cells of the immune system (6-9). On the other hand, this pathobiological process remains poorly understood and the physiological and biochemical factors that lead to cell death are still not clear. One main factor is the existing confusion between 'apoptosis' process, as compared and contrasted with 'necrosis', leading to the overlapping of the ante mortem changes, i.e. the process of cell death, and the post-mortem changes, i.e. the necrosis process.

Journal of Cellular and Molecular Medicine, 2007

Cell death is clearly an important factor in development, homeostasis, pathology and in aging, but medical efforts based on controlling cell death have not become major aspects of medicine. There are several reasons why hopes have been slow to be fulfilled, and they present indications for new directions in research. Most effort has focused on the machinery of cell death, or the proximate effectors of apoptosis and their closely associated and interacting proteins. But cells have many options other than apoptosis. These include autophagy, necrosis, atrophy and stepwise or other alternate means of self-disassembly. The response of a cell to a noxious or otherwise intimidating signal will depend heavily on the history, lineage and current status of the cell. Many metabolic and other processes adjust the sensitivity of cells to signals, and viruses aggressively attempt to regulate the death of their host cells. Another complicating factor is that many deathassociated proteins may have functions totally unrelated to their role in cell death, generating the possibility of undesirable side effects if one interferes with them. In the future, the challenge will be more to understand the challenge to the cell from a more global standpoint, including many more aspects of metabolism, and work toward alleviating or provoking the challenge in a targeted fashion.

Biology

The former conventional belief was that cell death resulted from either apoptosis or necrosis; however, in recent years, different pathways through which a cell can undergo cell death have been discovered. Various types of cell death are distinguished by specific morphological alterations in the cell’s structure, coupled with numerous biological activation processes. Various diseases, such as cancers, can occur due to the accumulation of damaged cells in the body caused by the dysregulation and failure of cell death. Thus, comprehending these cell death pathways is crucial for formulating effective therapeutic strategies. We focused on providing a comprehensive overview of the existing literature pertaining to various forms of cell death, encompassing apoptosis, anoikis, pyroptosis, NETosis, ferroptosis, autophagy, entosis, methuosis, paraptosis, mitoptosis, parthanatos, necroptosis, and necrosis.

Oncogene, 1999

International Journal of Biochemistry Research & Review, 2019

Discussions about what is life continue to struggle; there are pros and cons for whether a virus is alive. However, an opposite thing – cell death – appears to be tantamount important and equally not-easygoing to define. Nevertheless, our current knowledge about eukaryotic cell death has made a long way and resulted in a fruitful outcome: starting from three types of cell death (type I, II and III which are mainly applicable to eukaryotic cells of organisms from the biological kingdom animalia) in 1970s, Nomenclature Committee on Cell Death has named already twelve cell death forms in 2018, including the above mentioned apoptosis, autophagy and necrosis among them. How the scientific attitude towards cellular demise evolved and various aspects of different cell death modes are reviewed in this article.

Asian Journal of Animal and Veterinary Advances, 2015

The normal cell has its own homeostatic mechanism. A slight deviation in this mechanism leads firstly to an adaptive response in the form of hypertrophy, atrophy etc. But sometimes when adaptive response exceeds a limit also culminates to cell injury which ultimately leads to cell death. Irreversible form of cell injury leads to cell death in the form of necrosis, apoptosis and autophagy and by other alternative ways of necroptosis, anoikis, entosis and cornification. Necrosis and apoptosis are main mechanisms of cell death in mammalian cells. Necrosis is accidental, uncontrolled and un-programmed cell death which leads to cellular swelling, pyknosis, karyolysis, karyorrhexis, disruption of cell membrane and inflammation. Apoptosis is a programmed and energy dependent pathophysiological phenomenon leading to cellular shrinkage but no cell membrane rupture and no inflammatory response. Apoptosis can be mediated by extrinsic, intrinsic and perforin/granzyme pathways, leading to activation of execution caspases and finally protein cleavage, cross linking and DNA-fragmentation. Extrinsic pathway involve ligand (FasL, TNFα) and receptors (FasR, TNFR) interaction which bind to adapter proteins Fas Associated Death Domain (FADD) and TNFα Receptor Associated Death Domain (TRADD) with activation of initiator caspases-8. Intrinsic pathway involves cytochrome c release along with pro-apoptotic proteins and inhibits anti-apoptotic proteins, leads to cytochrome c interaction with Apaf-1, thus activation of pro-caspase-9. Overall, cell death have clarified many aspects of this fundamental process and brought to the attention of scientists its role in a large number of different diseases. The present review describes apoptosis and other alternate mechanisms of cell death with biomedical and veterinary perspectives.

Cell Death and Differentiation, 2005

Cell Death and Differentiation, 2009

2019

The balance of cell death and cell formation in multicellular organisms is crucial to maintain proper development, tissue hemostasis and immune regulation. Any dysregulation, at cellular and molecular level, results numerous pathologies. Cell death often evolve as host defense system, in response to pathogens, eliciting inflammation with certain molecular, cellular, biochemical, morphological and physiological changes through various cell death programs. This article reviews major types of cell death (apoptosis, autophagic cell death, necrosis and pyroptosis) as a host defense factor or mediated by inflammation.

International Journal of Cell Biology, 2014

Pathology - Research and Practice, 1996

In all normal tissues, cell proliferation and cell death are balanced. The physiology of normal cell death, which has become generally known as apoptosis or programmed cell death, has been intensely investigated in recent years. In this review the cell biology and biochemistry of apoptosis are discussed. Although apoptotic cells can be morphologically recognized, characteristic molecular features such as internucleosomal DNA fragmentation, and histochemical techniques such as in situ end labeling, facilitate the recognition of apoptosis. Many of the genes involved in the regulation of apoptosis, which include cell growth associated genes such as c-myc and p53, have been identified. It has become clear that the bcl-genes (more explicitly bcl-2 and bax) are important apoptosis regulators. The details of the mechanism of programmed cell death are, however, not completely unraveled.