Roles of p97 in protein quality control. Upper left: p97 extracts unfolded or misassembled secretory and membrane proteins from the ER. Concomitant with extraction, substrates are conjugated with ubiquitin (green circle with U). Upper right: ribosomes that stall during translation are disassembled into 40S +60S by an upstream factor. The ubiquitin-conjugated nascent chain remains attached to tRNA and passes through the exit tunnel (dotted segment). p97 recognizes these complexes and releases the nascent chain from the ribosome. Lower left and right: protein and protein-RNA aggregates require p97 for metabolism. p97 may either disassemble aggregates so that the proteasome can degrade them (lower left), or the aggregates can be packaged into autophagosomes (lower right) for delivery to the lysosome. p97 is required for an undetermined step in autophagosome maturation.