A Look into the Heart of Cellular Waste Disposal
Published:03 Aug.2023    Source:Max-Planck-Gesellschaft
Have you ever put off cleaning the house or decluttering the overflowing basement? Living cells cannot afford this procrastination when it comes to clearing the decks. Tiny garbage chutes are constantly active there to capture worn-out proteins, faulty cell components, or defective organelles. These garbage chutes, called autophagosomes, pick out the discarded components before they accumulate in the cell and cause damage. The cellular waste is then passed on to the cell's own recycling machinery, the lysosome, where it is digested and recycled.
Autophagy is a highly complex process involving many different proteins and protein complexes. Alex Faesen and his team has now succeeded, for the first time, in producing all the proteins involved in the autophagy process in the laboratory and observing them directly as the autophagosomes assemble. In the first step, the scientists produced each individual protein component in the laboratory. In the next step, the team brought the individual protein complexes together. To make autophagosomes, the autophagy initiation complex first creates a junction between a particular structure of the cell, the endoplasmic reticulum, and the autophagosome that forms.
But what starts the assembly of the autophagy machine, what starts it and what stops it? The researchers did not find a molecular "on" and "off" switch as in other molecular machines. Instead, the switch uses a highly unusual behavior of proteins: metamorphosis. Certain molecules, called ATG13 and ATG101, have the ability to fold in different 3D structures, thereby changing its ability to bind to proteins in the machine. This protein metamorphosis also gives the go-ahead for the assembly of the autophagy initiation complex at the right time and in the right place. Without metamorphosis, the initiation machine does not assemble.