How does impairment of autophagy lead to diseases? Ultrastructural analyses of the mutant mice revealed a marked accumulation of swollen and deformed mitochondria in the mutant hepatocytes [133] , pancreatic β cells [143, 144] , cardiac and skeletal myocytes [140, 141] and neurons [138] , but also the appearance of concentric membranous structures consisting of ER or sarcoplasmic reticulum in hepatocytes [133] , neuronal axons [137, 139] and skeletal myocytes [141] , as well as an increased number of peroxisomes and lipid droplets in hepatocytes [133, 148] . In addition to the accumulation of aberrant organelles, histological analyses of tissues with defective autophagy showed the amassment of polyubiquitylated proteins in almost all tissues (although the level varied from one region to another) forming inclusion bodies whose size and number increased with aging [149] . Consequently, basal autophagy also acts as the quality control machinery for cytoplasmic organelles (Figure 3(a) ). Although this could be partially achieved by bulk autophagy, these observations point to the existence of selective types of autophagy, a notion that is now supported by experimental data.