Recently it has become clearer that defects in protein turnover contribute to cancer and neurodegenerative diseases. Whereas the ubiquitin-proteasome system plays crucial roles in the selective and regulated proteolysis, autophagy, whose primary role is to supply amino acids in nutrient-poor conditions, is also important for constitutive degradation of cytoplasmic components. In fact, autophagy-deficiency in mice leads the formation of ubiquitin-positive inclusions, resulting in neurodegeneration and liver dysfunctions even in nutrient-rich conditions. Recently, we found that selective turnover via autophagy is important for liver homeostasis. We aim to clarify the physiological roles of constitutive autophagy, and its selectivity for target proteins.
