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Important new insights into the function of a key autophagy protein

Cancer Research UK Edinburgh Centre scientists provide new insights into the regulation and function of ATG16L1 – a key autophagy protein: April 2019

ATG16L1 harbours an intrinsic ability to bind autophagy related membranes through direct interaction with phosphatidylinositol‐3‐phosphate (PI3P).
ATG16L1 harbours an intrinsic ability to bind autophagy related membranes through direct interaction with phosphatidylinositol‐3‐phosphate (PI3P).

Autophagy is a highly conserved process induced under various conditions of cellular stress. It prevents cell damage and promotes survival in the event of energy or nutrient shortage. It can also constitute part of the cellular response to various cytotoxic insults. Thus, autophagy has primarily cytoprotective functions and needs to be tightly regulated to respond correctly to the different stimuli that cells experience, thereby conferring adaptation to the ever-changing environment.

It is now apparent that autophagy is deregulated in the context of various human pathologies, including cancer and neurodegeneration, and its modulation has considerable potential as a therapeutic approach. Unfortunately, although autophagy has been intensely studied over recent years, its mechanisms and regulation remain insufficiently understood. It is known that autophagy involves creation of membranous structures called autophagosomes but the details of this process remain elusive.

In a recent issue of the EMBO Journal researchers from the Cancer Research UK Edinburgh Centre and their collaborators provide important new insights into the regulation and function of the core autophagy protein ATG16L1. The study titled “Intrinsic lipid binding activity of ATG16L1 supports efficient membrane anchoring and autophagy” was driven by Leo Dudley, a PhD student, and led by Dr Noor Gammoh – “Brain Cancer Survival Pathways” laboratory. The authors identified key new events essential for autophagosome biogenesis involving the binding of ATG16L1 to phosphoinositides on the pre‐autophagosomal membrane, thus promoting autophagosome maturation. They identified a site on the coiled‐coil domain of ATG16L1 required for binding to phosphatidylinositol‐3‐phosphate and other phosphoinositides. These findings expand our understanding of autophagosome formation and are expected to have significant impact on future autophagy research.

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