Historical landmarks of autophagy research.

The year of 2013 marked the 50th anniversary of C de Duve's coining of the term "autophagy" for the degradation process of cytoplasmic constituents in the lysosome/vacuole. This year we regretfully lost this great scientist, who contributed much during the early years of research to the field of autophagy. Soon after the discovery of lysosomes by de Duve, electron microscopy revealed autophagy as a means of delivering intracellular components to the lysosome. For a long time after the discovery of autophagy, studies failed to yield any significant advances at a molecular level in our understanding of this fundamental pathway of degradation. The first breakthrough was made in the early 1990s, as autophagy was discovered in yeast subjected to starvation by microscopic observation. Next, a genetic effort to address the poorly understood problem of autophagy led to the discovery of many autophagy-defective mutants. Subsequent identification of autophagy-related genes in yeast revealed unique sets of molecules involved in membrane dynamics during autophagy. ATG homologs were subsequently found in various organisms, indicating that the fundamental mechanism of autophagy is well conserved among eukaryotes. These findings brought revolutionary changes to research in this field. For instance, the last 10 years have seen remarkable progress in our understanding of autophagy, not only in terms of the molecular mechanisms of autophagy, but also with regard to its broad physiological roles and relevance to health and disease. Now our knowledge of autophagy is dramatically expanding day by day. Here, the historical landmarks underpinning the explosion of autophagy research are described with a particular focus on the contribution of yeast as a model organism.