Elucidating the role of a multisubunit tethering complex-exocyst in autophagosome biogenesis

Abstract

Inside a cell, there is constant synthesis and degradation of cytosolic components such as various proteins, organelles, supramolecular assemblies including cytoskeleton, ribosomes and intracellular vesicles. This dynamic equilibrium is affected by cell intrinsic (organelle damage, signalling, etc.) and extrinsic (nutrient availability, temperature, pH, mitogens, pathogens, etc.) changes. Adaptation to such conditions is achieved by maintaining cellular homeostasis in which the rates of synthesis and degradation of components are modulated in order to maintain cellular health, thereby promoting its viability. In this context, proteolysis, the turnover of proteins, plays a role in regulating several key cellular events including cell cycle, receptor mediated endocytosis, signal transduction, adaptation to stress, etc. (Ciechanover, 2005). The two major pathways contributing in maintenance of cellular proteostasis are: 1) ubiquitin proteosome system (Driscoll and Goldberg, 1990), and 2) lysosomal mediated degradation (De Duve, 1963; De Duve et al., 1955). A major difference in mode of action of these two pathways is that individual proteins are degraded by proteasome (Finley, 2009) while lysosomal degradation aids in bulk protein degradation (Luzio et al., 2007). The smaller pore size of proteasome limits the degradation of larger cargo like protein complexes or aggregates (Finley, 2009). Such bulk cargo is degraded in lysosome (vacuoles in yeast) through a pathway known as autophagy.