Axe et al. identify a cellular nursery for the membrane pouches that perform autophagy. Cao et al. reveal a method for pinning down the activity of autophagy control proteins.
During autophagy, a membrane container called an autophagosome scoops up some of the cell's contents, which the lysosome then digests. This cannibalism not only recycles nutrients for famished cells, it helps purge marred proteins. Too little or too much autophagy might cause illnesses such as Alzheimer's disease and certain types of cancer.
A stubborn mystery is where the autophagosome membrane comes from. Does it derive from the endoplasmic reticulum, as many scientists think? Or does it form when lipids in the cytoplasm rendezvous? Axe et al. attacked the question by tracking a phospholipid named PI(3)P that's essential for making an autophagosome. In starving cells a bud rich in PI(3)P bulged from the ER. This outgrowth, which the researchers dubbed an omegasome, spawned autophagosomes. The team observed new autophagosomes appearing inside the omegasome and then breaking free. Whether the omegasome separates from the ER or remains attached is unclear, the researchers say. But they conclude that the results support an ER origin for the autophagosome.
More than 20 proteins collaborate to orchestrate autophagy, but researchers are still trying to work out each protein's job. Instead of following the typical strategy of eliminating two or three of these proteins, Cao et al. went whole hog, deleting all 24 of the known yeast autophagy proteins. The team then added back different combinations of proteins to test hypotheses about their functions. For example, previous work suggested that the protein Atg17 is a pioneer that draws other proteins to the developing autophagosome. However, the researchers found that two other proteins are also necessary to instigate autophagosome formation.