Apoptosis and autophagy

Apoptosis and autophagy are highly coordinated mechanisms to maintain cellular homeostasis against various intrinsic and/or extrinsic stresses in eukaryotic cells. Since the early 1990s, our knowledge of the molecular mechanisms and the physiological functions of apoptosis have increased substantially. Dysfunction of apoptosis leads to various diseases, including cancers and degenerative diseases. Therefore, small molecules that induce apoptosis or synthetic lethality with mutated genes have been examined for the development of cancer-specific apoptosis-inducing agents; conversely, small molecules that suppress apoptosis have been identified for protective agents against neuronal cell death. On the other hand, autophagy is an evolutionarily conserved pathway involved in the degradation of intracellular components and is critical for the maintenance of cellular homeostasis. The mechanisms and functions of autophagy have been revealed by genetic studies in yeast, which identified a series of autophagy-related genes. Many small molecules that have been discovered to induce or inhibit autophagy also provide insight into the mechanisms and functions of the autophagic process. In this chapter, we introduce several small molecules identified by synthetic lethality screening, apoptosis inhibitors, and autophagy modulators.