By identifying a protein that hampers membrane trafficking within the cell, Longatti et al. provide evidence that recycling endosomes supply membrane to growing autophagosomes.
When cells are stressed or hungry, they often eat some of their contents through the process of autophagy, in which a membrane compartment called an autophagosome forms and scoops up cytoplasmic material for digestion. Autophagy's early steps remain a puzzle, however. Previous studies have identified several origins for the autophagosome membrane, including the ER and mitochondria. Longatti et al. identify a new source—recycling endosomes, which shuttle cargo from early endosomes to the cell membrane.
The researchers started out by searching for proteins that control the early stages of autophagy. They screened potential inhibitors of Rab GTPases, which help manage membrane movement within the cell and are essential for several steps of autophagosome development. The team then tested which of the 11 inhibitors they identified linked up with the autophagosome protein ULK1. One protein, TBC1D14, combined with ULK1 on recycling endosomes.
Longatti et al. discovered that a Rab GTPase on recycling endosomes, Rab11, promotes autophagy. TBC1D14 blocked autophagy by binding to Rab11 and deforming the recycling endosomes into tubes that cannot dispatch membrane to an autophagosome. When a cell is starving, TBC1D14 relocates from the recycling endosomes to the Golgi apparatus, allowing autophagy to proceed.