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De novo lipogenesis fuels adipocyte autophagosome membrane dynamics

Authors :
Leslie A. Rowland
Adilson Guilherme
Felipe Henriques
Chloe DiMarzio
Nicole Wetoska
Mark Kelly
Keith Reddig
Gregory Hendricks
Meixia Pan
Xianlin Han
Olga R. Ilkayeva
Christopher B. Newgard
Michael P. Czech
Publication Year :
2022
Publisher :
Cold Spring Harbor Laboratory, 2022.

Abstract

SummaryAutophagy is a homeostatic degradative process for cell components that enables stress resilience and can determine cellular fate and function. However, lipid sources for the rapid membrane expansions of autophagosomes, the workhorses of autophagy, are poorly understood. Here, we identify de novo lipogenesis (DNL) as a critical source of fatty acids (FA) to fuel autophagosome dynamics in adipocytes. Adipocyte fatty acid synthase (Fasn) deficiency markedly impairs autophagy, evident by autophagosome accumulation, and severely compromises degradation of the autophagic substrate p62. Autophagy dependence on FA produced by Fasn is not fully alleviated by exogenous FA in cultured adipocytes even though lipid droplet size is restored. Imaging studies reveal that Fasn colocalizes with nascent autophagosomes, while loss of Fasn decreases certain membrane phosphoinositides known to be required for autophagosome assembly. Together, our studies highlight a newly appreciated function for adipocyte DNL in autophagosome membrane formation and provide evidence that localized FA synthesis contributes to autophagosome dynamics.

Details

Database :
OpenAIRE
Accession number :
edsair.doi...........37cdc662341aa004ce31ddde51ee9278
Full Text :
https://doi.org/10.1101/2022.05.25.493413