Dynamin-2 facilitates Atg9 recycling from nascent autophagosomes
Preprint posted on January 06, 2018 https://www.biorxiv.org/content/early/2018/01/06/241901
Autophagy is an intracellular recycling process that removes damaging material, such as protein aggregates, dysfunctional mitochondria and invading pathogens, for eventual destruction and reuse of the constituent components. As such, autophagy protects us from diseases, including cancer and neurodegeneration. Autophagy involves the formation of a large vesicle that engulfs cargo for destruction in the lysosome and this is accompanied by the action of a series of autophagy machinery proteins. Atg9 is the only transmembrane protein within the autophagy related genes, and Atg9-containing vesicles are thought to deliver membrane and/or important proteins to the growing autophagosome membrane through ‘kiss and run’ interactions. However, in mammals, Atg9 itself is not incorporated into the autophagosome but is instead recycled. How Atg9 avoids incorporation into the autophagosome and destruction is unknown.
The authors of this preprint investigated the role of Dynamin-2 in autophagy. Dynamins are GTPases that mediate membrane scission during the formation of vesicles, most famously during endocytosis. They found that Dynamin-2 colocalises with autophagosome proteins and loss of Dynamin-2 function by means of genetic knockout, siRNA depletion or chemical inhibition increases the colocalisation of Atg9 with autophagosomes. Most interestingly, in the absence of Dynamin-2, Atg9 was re-routed to degradative lysosomes, where it was destroyed. The authors conclude that Dynamin-2 facilitates the removal of Atg9 from the growing autophagosome membrane.
“Blocking Atg9 recycling by interfering with Dynamin-2 helps retain Atg9 in autophagosomes and degrades Atg9 by autophagy.”
What I like about this work
This study could answer how the poorly understood and core autophagy protein Atg9 is recycled during autophagy for continual use.
This work raises some fascinating questions. It would be exciting to see if Dynamin-2 is involved in generating the reservoir of Atg9 vesicles that contribute to autophagosome formation, perhaps derived from endosomes and the Golgi. Are there BAR domain-containing proteins that act in concert with Dynamin-2 at the forming autophagosome? Can our cells run out of Atg9 vesicles if Dynamin-2 is dysfunctional?
Posted on: 27th February 2018Read preprint
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