Autophagy unveiled

In cell biology research it seems that building gets more attention than destruction: work on the cell cycle leapt ahead while apoptosis research was in its infancy, and protein synthesis pathways were well established when autophagy was, for most researchers, a word that drew blank stares.

Thus the molecular description of autophagy is a relatively recent phenomenon (Klionsky and Emr, 2000). But the morphology came early. Autophagy is the destructive process in which a double membrane envelops cytoplasm and organelles before targeting them to lysosomes for destruction. It was first spotted in differentiating kidney cells as they redirected their metabolic energies (Clark, 1957).

A robust model was established by Ashford and Porter (1962), who spotted autophagy when glucagon was perfused into rat livers. Glucagon is made in response to low blood sugar levels, so autophagy may be the cell's way of scaling back operations in hard times. In the words of Ashford and Porter (1962), the hydrolysis may be “providing the protoplast with breakdown products for use in a reoriented physiology,” with the membrane “shield[ing] the rest of the cell from the general spread of the degradative process.”

The word autophagy crept into the literature in the 1960s (Deter et al., 1967) as it became clear that the process intersected with but was distinct from other forms of lysosomal degradation. The endoplasmic reticulum was proposed as the source of the autophagic membranes (Dunn, 1990), although uncertainties about this and other details of autophagy remain.