Figure 2

Schematic presentation of induced autophagy and basal (constitutive) autophagy. Under nutrient-rich conditions, autophagic proteolysis proceeds in hepatocytes at a basal rate (top panel, pink zone), which is enhanced two- to threefold to an induced rate under nutrient-starvation conditions (blue zone). When animals are re-fed, the rate of autophagic proteolysis promptly returns to the basal level. In contrast to the liver, autophagy in the brain is thought to proceed at a basal rate, irrespective of nutrient conditions. However, this basal or constitutive autophagy plays a critical role in the quality control system of neurons. Rapamycin and its homologs, which upregulate autophagy to an induced level (bottom panel, broken line), are expected to prevent the accumulation of aggregate-prone proteins. It should be noted that autophagic activity declines with age, which may relate to the age-dependent onset of neurodegenerative diseases