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Autophagy derives from the Greek words auto (self) and phagia (eating) and is a term that quite aptly describes the process of self-eating, or consumption and digestion of the cell's own constituents (Ref. 1). If in anthropomorphic terms apoptosis is used as a term to describe cell suicide, by analogy, autophagy could be envisioned as a form of self-cannibalism. Autophagy is but one of the mechanisms the cell has at its disposal to degrade intracellular proteins. Although there are many protein degradation (proteolytic) systems in cells, the two major ones are the ubiquitin-proteasome system (UPS) and the autophagy-lysosome pathway (ALP). These degradation systems are important for the normal turnover of cell components both under normal housekeeping conditions and under conditions of stress. Such turnover is important for the renewal of the cell and the removal of potentially damaging constituents, but also for fine-tuning the cell phenotype, so that it can respond more readily to changes in its environment and its own metabolic changes.
The ALP differs from the UPS in a number of ways, most notably because degradation through the ALP is relatively more important for long-lived proteins, and because the ALP can also degrade cellular organelles through the process of macroautophagy, not only smaller proteins. Macroautophagy is one of the three major avenues through which the ALP degrades intracellular constituents, the other two being chaperone-mediated autophagy (CMA) and microautophagy. All three pathways result in delivery of intracellular components to the lysosomes; within this acidic environment, and through the effects of lysosomal hydrolases, they are digested into their composite parts, which can then be reused by the cell. In this way, the cell can reorganise its arsenal to best fit its needs.
What distinguishes the different types of autophagy is the manner in which the cellular constituents reach the lysosomes. In microautophagy, invaginations are formed at the level of the lysosomal membrane; such invaginations engulf neighbouring areas of the cytosol, which may include organelles, lipids or proteins (Ref. 2). The invaginations eventually round up into vesicles that are digested within the lysosomes, together with their engulfed constituents. The lysosomal membrane itself can be engulfed in this manner, leading to the adjustment of the size of the vacuole. Very little...