Autophagy is generally considered as a process to supply nutrients by self-digestion for cells to survive starvation. However, autophagy, along with the proteasome system, is also involved in the turnover of cellular components under normal conditions.
While proteasomes target and selectively degrade ubiquitinated proteins, autophagy degrades all the contents engulfed by autophagosomes, and, therefore, is called “the bulk degradation system.” In addition, selective autophagy pathways target cellular organelles, such as mitochondria and peroxisomes. These degradation mechanisms are respectively known as “mitophagy” and “pexophagy.” Various other autophagic mechanisms are also under investigation.
When a cell is placed under starvation conditions, a flat vesicle called an isolate membrane appears in the cytoplasm (1). Subsequently, the membrane extends while taking in the cytoplasm (2), its edges fusing to compose an autophagosome (AP) (3). Mitochondria and other large organelles are also contained within the AP. When the AP fuses with a lysosome (4), its contents are degraded (5). The amino acids gained through autodigestion are reused as nutrient sources. It is not known at this time how the isolate membrane appears or how its components are obtained.
Although in the limelight in recent years, autophagy was first observed by electron microscopy over 40 years ago. Nevertheless, functional studies of autophagy did not progress rapidly because factors involved in the process remained unknown for a long period of time.
Dr. Yoshinori Ohsumi (currently of the Tokyo Institute of Technology) and his colleagues at the National Institute for Basic Biology isolated yeast strains that were unable to degrades the contents of autophagosomes, and successfully cloned the autophagy-related (APG/ATG) genes (Tsukada and Ohsumi, 1993). As of 2016, the number of ATG genes in budding yeast stands at 41. Many of these genes are conserved in mammals and plants (the amino acid sequence homology among species is limited, but the 3D structures are similar).
With the discovery of APG/ATG genes, functions of the gene products have been extensively studied, and details of the mechanism and physiological role of autophagy are being elucidated one after another.