The autophagy protein ATG9A enables lipid mobilization from lipid droplets.

The multispanning membrane protein ATG9A is a scramblase that flips phospholipids between the two membrane leaflets, thus contributing to the expansion of the phagophore membrane in the early stages of autophagy. Herein, we show that depletion of ATG9A does not only inhibit autophagy but also increases the size and/or number of lipid droplets in human cell lines and C. elegans. Moreover, ATG9A depletion blocks transfer of fatty acids from lipid droplets to mitochondria and, consequently, utilization of fatty acids in mitochondrial respiration. ATG9A localizes to vesicular-tubular clusters (VTCs) that are tightly associated with an ER subdomain enriched in another multispanning membrane scramblase, TMEM41B, and also in close proximity to phagophores, lipid droplets and mitochondria. These findings indicate that ATG9A plays a critical role in lipid mobilization from lipid droplets to autophagosomes and mitochondria, highlighting the importance of ATG9A in both autophagic and non-autophagic processes. © 2021. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

Citation

Elodie Mailler, Carlos M Guardia, Xiaofei Bai, Michal Jarnik, Chad D Williamson, Yan Li, Nunziata Maio, Andy Golden, Juan S Bonifacino. The autophagy protein ATG9A enables lipid mobilization from lipid droplets. Nature communications. 2021 Nov 19;12(1):6750

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PMID: 34799570

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