Autophagy receptors don't "recruit" membranes, the membranes recruit autophagy receptors

What is it about?

Autophagy is the 'clean-up crew' of the cell – used by cells to break-down debris like broken proteins, bits of cell membrane, viruses or bacteria. To capture this trash, cells use specialized membranes to selectively trap the cargo for recycling. Almost every drawing of this process has three key things in common; Cargo that requires degradation, membranes to trap the cargo, and "selective autophagy receptors" bridging the divide between them. It has been drawn this way for almost a decade, because selective autophagy receptors have to specific regions. The first region lets them bind to a cargo, and varies between each autophagy receptor. The second region is a "LIR motif", which allows them to bind to the Atg8 proteins (known as LC3s and GABARAPs in mammals) on autophagosomal membranes. This paper shows that we may have been drawing the model back-to-front the entire time. The autophagy receptors don't recruit the membranes from somewhere else in the cell. In fact, the LIR motif in an autophagy receptor isn't required for Atg8 protein recruitment at all. The Atg8 proteins on autophagosomal membranes actually recruit more autophagy receptors. The additional autophagy receptors trigger the same process required to promote membrane formation after cargo detection, but this time there's a twist. As the membranes grow, they gain more Atg8 proteins to recruit even more of the autophagy receptors, which makes the membranes grow even faster to recruit even more autophagy receptors. This cascade of membrane growth is essential for efficient autophagy.

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Why is it important?

This paper redefines our understanding of why selective autophagy receptors have a LIR motif. It also finally explains why some autophagy receptors don't even have one. We have discovered an entirely new mechanism of autophagy receptor recruitment which amplifies selective autophagy, and found the first rational explanation for how the Atg8 proteins regulate autophagosome size and biogenesis efficiency.

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