AUTOPHAGY AND INFLAMMASOME

Reciprocal between Autophagy and Inflammasome Activation

By

Table of Contents

Background3

Overview of Autophagy5

Overview of Inflammasome6

Impact of Autophagy on Inflammasome Activation7

Reduction in il-1ß8

Reduction in Caspase-19

Role of NLRC4 and Mitochondrial DNA in Activation of Inflammasome9

References11

Reciprocal between Autophagy and Inflammasome Activation

Background

According to medical dictionary, autophagy is a biological process of self digestion by a cell by way of the action of enzymes originating under the same cell. The process of autophagy generally involves four steps. These include induction of autophagy, autophagosome formation, degradation, and reuse. Nutrient starvation is considered as the most likely trigger for autophagy. Autophagy can be inducted in mammals, as well as, yeast and plants. In mammals, the induction of autophagy is a complex process that involves the role of amino acids. The depletion of total amino acids takes place that induces autophagy in various types of cultured cells.

The next step, after autophagy induction, is autophagosome formation in which cytoplasmic constituents, including organelles, are seized by a special membrane called the isolation or phagophore membrane. This step is a simple sequestration, and no degradation occurs. In the proceeding step, autophagosomes and lysosomes get fused with one another. The inner layers of the combination get degraded through by lysosomal hydrolases. Enzymes play a significant role in this degradation, and the most benefitting enzyme is yeast Atg15/Aut5/Cvt17, which is a putative lipase. These degrading structures are often called “autolysosomes” or “autophagolysosomes.” The last step in the autophagy process is of resuing. In this step, the degraded macromolecules in the lysosome are exported to the cytosol for the purpose of reuse.

On the cellular level, the autophagy begins with the formation of a vacuole and receiver that extends from a non-selective component of the cytoplasm. This thus forms autophagosome that is bounded by a double membrane phospholipid (Egan et al. 2011). Several cellular compartments (endoplasmic reticulum, Golgi apparatus and trans-Golgi network) and the plasma membrane probably participate in the formation of the autophagosome. Fifteen Atg proteins are required for its biogenesis. With the exception of Atg9, these proteins have no trans-membrane domain. Atg proteins, recruited in the cytoplasm, complexed with each other and associate transiently with the membrane pre-autophagosomale and that of the autophagosome.

Accumulation of a large number of damaged macromolecules and organelles are common to all senescent cell features. Basic biological process ensuring the destruction of cellular debris is autophagy (Okamoto & Kondo-Okamoto, 2012). When autophagy damages organelles, they are captured as autophagosome which are then fuse with lysosomes. When autophagy macromolecules and fragments of cell membranes capture lysosome, the chaperone-dependent autophagy and damaged proteins are transported into the cavity of the lysosomes with special chaperone proteins (such as Hsp73). If such clean cellular garbage does not occur or it is not effective, it may be the cause of aging and cell death (Gross et al. 2011 ). Violations of autophagy often cause a number of diseases in the older years. The activation of autophagy in different models (C. elegans, S. cerevisiae, D. Melanogaster, M.musculus) leads to an increase in life expectancy of experimental ...