The “macroautophagic” pathway responds to stimulation by various environmental cues including nutrient availability or noxious agents, which result in the accumulation of damaged proteins and/or organelles as well as pathogenic bacteria or viral infection. In the nucleation phase, a preautophagosomal structure develops from subcellular membranes and subsequently evolves into the phagophore or isolation membrane. The isolation membrane then expands to surround and engulf a cytoplasmic “cargo” of material targeted for degradation, culminating in double-membraned autophagosomes. Finally, the fusion of autophagosomes with lysosomes results in the formation of the autolysosome. During the degradative phase of autophagy, the encapsulated contents of autolysosomes are digested by lysosomal degradative enzymes (e.g., cathepsins and other acid hydrolases). The digested contents are then released to the cytosol for reutilization in anabolic pathways.
