Regulation of autophagic flux via dynamic trafficking of the SNARE Stx17: studies using a chemical biology approach

Abstract

Macroautophagy (herein autophagy) is a major intracellular pathway that is indispensable for maintaining cellular homeostasis. Autophagy has been evolutionarily conserved in organisms ranging from yeast to humans. The word autophagy, which is Latin for self-eating, was first coined by Christian de Duve (Deter et al., 1967). He identified autophagy as a process of self-cannibalization which involves sequestration of cellular components within double membrane structures called autophagosomes, which then fuse with lysosomes to form autolysosomes wherein complex macromolecules are degraded and recycled for cellular use. The rate at which dynamic turnover of cellular components occurs by the process of autophagy is called ‘autophagic flux’. Basal level of autophagy occurs in all cells and tissues, and is indispensable for maintaining cellular homeostasis by protein and organelle turnover (Mizushima et al., 2004; Musiwaro et al., 2013). Cellular stresses such as nutrient starvation, pathogen invasion, organellar damage and protein aggregation can increase levels of autophagy as an adaptive stress response. As autophagy is central to maintaining cellular homeostasis, dysfunctional autophagy has been attributed to a variety of major human disease such as cancer, neurodegeneration and cardiovascular diseases (Jiang and Mizushima, 2013).