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Autophagy, is a highly conserved self-degradative mechanism. This cellular process is responsible for the delivery of damaged and superfluous cellular components, invading pathogens as well as protein aggregates to the lysosome for catabolism. Autophagy is by-and-large cytoprotective, as it allows for the recycling of dysfunctional and toxic cellular components into... read moretheir basic building blocks. These can, in turn, be utilized for energy provision or biosynthesis. Autophagy is constantly ongoing in all eukaryotic cells, and aids in cellular housekeeping. During metabolic stress, autophagy can be up-regulated and acts as an adaptive response system essential for cell survival, and the maintenance of energetic balance. Three general types of autophagy have been described: micro¬autophagy, chaperone-mediated autophagy (CMA) and macroautophagy. They differ mainly in the way substrates are delivered to the lysosome for degradation.
Lysosomes are catabolic organelles responsible for the degradation of extracellular and intracellular materials for the regeneration of basic building blocks, cellular housekeeping, or pathogen elimination. Due to their high acidity and enzyme abundance lysosomes are able to breakdown a wide range of substrates. Lysosomes also play a major role in cellular signalling as they possess the ability to sense and communicate cellular energetic state. Thus, lysosomes are emerging as major signalling hubs for nutrient homeostasis that extends beyond waste disposal and building block recycling.
Deficiencies in the autophagy-lysosome system usually result in the collapse of cellular homeostasis and tissue dysfunction. Indeed, this process is implicated in the pathogenesis of a myriad of conditions including: neurodegenerative disease, muscular dystrophies, metabolic disorders, cancer, cardiovascular disease as well as aging. Moreover, genetic deficiencies in lysosomal proteins result in lysosomal storage diseases (LSDs) a group early-onset debilitating multi-systemic degenerative diseases. Thus, the autophagy-lysosome system is a biological mechanism fast emerging as a vital cellular process with vast therapeutic implications. In many instances modulation of aberrant autophagy or enhanced lysosomal biogenesis has been proven sufficient to ameliorate symptoms and improve prognosis, thus setting the stage for the discovery of autophagy/lysosomal modulators with the purpose of treating disease.