An Overview of Cell Death Types (I)

Posted January 1, 2021 by Bonnibelle

Cell death often occurs in normal tissues, which is necessary to maintain tissue function and morphology, including programmed death and passive cell death.

Cell death is the irreversible cessation of life phenomena and the end of life. Cell death often occurs in normal tissues, which is necessary to maintain tissue function and morphology, including programmed death and passive cell death.
1 The programmed death
Programmed cell death is a ubiquitous process in the development of organisms. It is an active and orderly way of cell death determined by genes. When cells are stimulated by internal and external environmental factors, they regulate the suicide protection measures initiated by genes, including the activation of some molecular mechanisms and gene programming. In this way, unnecessary cells or cells that are about to be specialized are removed from the body.
1.1 Apoptosis
Apoptosis refers to the autonomous and orderly death of cells regulated by genes in order to maintain the stability of the internal environment, also known as programmed cell death. Apoptosis is an active process that involves the activation, expression and regulation of a series of genes. It is a death process that is actively taken to better adapt to the living environment. It plays an important role in the evolution of organisms, the stability of the internal environment, and the development of multiple systems, and the disorder of the apoptotic process may be directly or indirectly related to the occurrence of many diseases. The pro-apoptotic substances involved in cell apoptosis include Bcl-2 protein family, Cyt C, apoptosis-inducing factor (AIF), Caspase family and Smac protein.
The Bcl-2 protein family is a special family, mainly located on the mitochondria, endoplasmic reticulum and continuous perinuclear membrane. Some of its members promote cell apoptosis, such as Bdd, Bid, Bax, Bak, and some members prevent cell apoptosis. Death, such as Bcl-2, Bcl-x, Bcl-w. The pro-apoptotic proteins Bax and Bak are located on the outer mitochondrial membrane, where they can form release pores, leading to enhanced mitochondrial membrane permeability, allowing soluble proteins in the interstitial space to enter the cytoplasm, and then induce cell apoptosis. Under the stimulation of apoptosis signals, the corresponding pro-apoptotic proteins will undergo conformational changes to form corresponding oligomers, and the pro-apoptotic oligomers will be integrated into the mitochondrial outer model to form new pores allowing Cyt C to be released from the mitochondria.
Cyt C: Under normal circumstances, Cyt C exists in the mitochondrial membrane space and participates in electron transmission in the mitochondrial respiratory chain. Under normal circumstances, Cyt C cannot pass through the mitochondria, and is released to the cytoplasm to cause cell apoptosis when stimulated by the corresponding apoptosis signal. Cyt C is an important factor in the mitochondrial-mediated apoptosis pathway and plays an important role in the process of apoptosis.
Apoptosis-inducing factor (AIF): AIF is a conserved flavoprotein that exists in the outer mitochondrial membrane space. It has a dual function: it participates in electron transfer as a mitochondrial oxidoreductase under the normal physiological state of cells; when regulating apoptosis at this time, it is a major effector protein, which can directly mediate the apoptosis pathway independent of Caspase. When stimulated by apoptosis signals, it is released from the mitochondria, then enters the nucleus and acts independently on chromatin. Under the catalysis of related enzymes, it causes large-scale DNA fragmentation and chromatin condensation, which causes the cell to undergo apoptosis. Die. Once AIF is released into the cytoplasm, it will promote the release of Cyt C, thereby accelerating cell apoptosis. The release of AIF is regulated by anti-apoptotic proteins, which can reduce the release of AIF and slow down cell apoptosis. Although the release of AIF by mitochondria is independent of Caspase, related studies have shown that Caspase can enhance the permeability of mitochondrial membranes, thereby promoting the release of AIF by mitochondria.
Caspase family: The Caspase family is a group of proteases with similar structures that exist in the cytoplasm. They are closely related to the apoptosis of eukaryotic cells and participate in the regulation of cell growth, differentiation and apoptosis. Caspase exists as an inactive precursor under normal conditions and is activated when stimulated by certain accessory proteins. Caspase family is divided into three categories: apoptosis initiating factors, apoptosis executive factors and inflammatory mediators. There is also a certain cascade amplification effect in the process of cell apoptosis, which eventually leads to cell apoptosis. So far, 14 kinds of Caspase have been discovered, of which Caspase 9 is the initiator of apoptosis and Caspase 3 is the main executor of apoptosis. In addition, Caspase 6, 7, 8, and 10 all have the effect of promoting cell apoptosis.
Smac protein: Smac protein is a protein that exists in mitochondria and regulates cell apoptosis. Its pro-apoptotic effect is achieved by reversing the effect of inhibitor of apoptosis, especially X-linked inhibitor of apoptosis. When cells are stimulated by apoptosis, mitochondria release Smac protein into the cytoplasm and combine with apoptosis inhibitor protein, causing it to lose the effect of inhibiting Caspase activity, thereby promoting cell apoptosis. It is also an important apoptotic factor released at the same time as Cyt C.
1.2 Autophagy
Autophagy is an evolutionarily conserved lysosome- or vacuole-dependent catabolic pathway in
eukaryotes. Autophagy can be either selective or non-selective. Cells form autophagosomes by encapsulating the degraded products with double or multi-layer membrane, and then transport them to lysosomes to form autophagy lysosomes and degrade cytosolic substances by various enzymes. Autophagy contributes to maintaining the metabolic balance of cells, which is a mechanism of cell self-protection. Autophagy can be induced during nutritional deficiency, and can promote the utilization of nutrients and metabolites. It plays a vital role in the regulation of cell metabolism. Meanwhile, the metabolic status of cells affects autophagy in turn. Autophagy plays an important role in maintaining metabolic homeostasis. Metabolic balance and body development play an important role. Autophagy imbalance is related to a variety of mammalian diseases, including diabetes, neurodegeneration and cancer.
Autophagy is classified according to the different mechanisms by which metabolites enter the lysosome. There are three main types: macro-autophagy, chaperone-mediated autophagy and micro-autophagy.
To be continued in Part II…
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Categories Biotech
Last Updated January 1, 2021