There are two major pathways of intracellular protein degradation. First, the ubiquitin-proteasome system in the cytosol is involved in degradation of short-lived, damaged or misfolded proteins [1, 2]. Target proteins to be degraded are first tagged with ubiquitin and then digested by the proteasome with strict recognition by the ubiquitin ligase system. Long-lived proteins are believed to be degraded within a specific compartment, the lysosome/vacuole. So far several delivery routes to this lytic compartment have been proposed. The process of degradation of the cell’s own intracellular constituents in lysosomes is generally called autophagy in contrast to heterophagy, degradation of extracellular materials [3]. Macroautophagy (hereafter autophagy) is a major pathway in autophagy, and initiates by enwrapping a portion of cytoplasm by a membrane sac called the isolation membrane, to form a double membrane structure, the autophagosome [4]. The autophagosome then fuses with the lysosome, becoming the autolysosome and its inner membrane and contents are digested for reuse. Autophagy is characterized as being nonselective resulting in the bulk degradation of cellular proteins. More than 90% of cellular proteins are long lived, thus the turnover of long-lived proteins is important to understand the physiology of the cell. Since the lysosome was discovered [5], electron microscopy has revealed that autophagy occurs in a variety of cells from different tissues and cultured cells, and it is now generally accepted that autophagy is a ubiquitous activity in eukaryotic cells.

However, the molecular mechanism of autophagy has remained elusive. There was no specific monitoring marker or quantitative assay system to detect autophagy in mammalian cells. Therefore, the genes involved in autophagy remained unidentified for a long time. Here, we will focus on the recent progress in the molecular dissection of autophagy.