Ubiquitous déjà vu

How miserable must life get before one is ready to eat parts of one's own body? Most humans would probably rather starve to death. But nucleated cells are sometimes forced to gather food from their own interior in a process known as autophagy¹, to provide the nutrients needed to keep their vital functions running. However, severe starvation is only one of the factors that can trigger this grisly feast. Autophagy is also one of the main ways for a cell to get rid of obsolete parts, including aged proteins from the cytoplasm and even complete organelles. In busy cells such as those in the liver, for example, the mitochondria that produce chemical energy wear out rapidly and are subsequently digested by autophagy. For obvious reasons, autophagy must be strictly controlled, yet surprisingly few studies have addressed this problem. Now, however, on page 395 of this issue, Mizushima et al.² report the discovery of an intriguing protein-modification pathway that is required for autophagy. This pathway seems to be conserved from yeast to mammals, and may point to a general principle of protein targeting by covalent modification.

Autophagy is the bulk delivery of cytoplasmic material to the cell's central digestion organelles, the lysosomes¹. The process starts with the formation of double-membrane sheets, possibly derived from the endoplasmic reticulum, which envelop a portion of the cell's interior. This newly created vesicle, the autophagosome, seems to travel to the lysosomes along microtubules, which serve as guiding tracks³. On reaching the lysosome, the autophagosome fuses with it. Like our stomach, lysosomes are rather acidic inside, containing a battery of enzymes to break down cellular compounds. In this way, amino acids, lipids, sugars and nucleotides are recovered and transported back to the cytosol, where they can be re-used by the same cell.