Figure 1. Schematic depiction of PD-related genes associated with different autophagy pathways.

A large group of genes associated with familial and sporadic PD are strongly linked to macroautophagy, chaperone-mediated autophagy, mitophagy, and downstream lysosomal function. Macroautophagy, the main route of cellular degradation, is initiated from an isolated membrane (phagophore) forming the double membraned autophagosome to sequester cytosolic material. Subsequent fusion of autophagosomes with lysosomes forms the autolysosome for hydrolase-mediated degradation of its contents. In chaperone-mediated autophagy, the cytosolic chaperone protein HSC70 targets and translocates unfolded proteins directly to lysosomes through binding to the lysosomal receptor LAMP2A. Compared to non-selective/bulk macroautophagy, selective mitophagy labels only damaged mitochondria for downstream autophagic degradation. See text for more detailed description of PD gene-mediated effects on various types and steps of the autophagic-lysosomal pathway.