De novo lipogenesis fuels adipocyte autophagosome membrane dynamics
De novo lipogenesis fuels adipocyte autophagosome membrane dynamics
Summary Autophagy 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.
Henriques Felipe、DiMarzio Chloe、Kelly Mark、Hendricks Gregory、Czech Michael P.、Newgard Christopher B.、Wetoska Nicole、Pan Meixia、Reddig Keith、Rowland Leslie A.、Han Xianlin、Ilkayeva Olga R.、Guilherme Adilson
Program in Molecular Medicine, University of Massachusetts Chan Medical SchoolProgram in Molecular Medicine, University of Massachusetts Chan Medical SchoolProgram in Molecular Medicine, University of Massachusetts Chan Medical SchoolDepartment of Radiology, University of Massachusetts Chan Medical SchoolProgram in Molecular Medicine, University of Massachusetts Chan Medical SchoolDuke Molecular Physiology Institute, Department of Medicine, Division of Endocrinology, Metabolism and Nutrition, Duke University School of MedicineProgram in Molecular Medicine, University of Massachusetts Chan Medical SchoolBarshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San AntonioDepartment of Radiology, University of Massachusetts Chan Medical SchoolProgram in Molecular Medicine, University of Massachusetts Chan Medical SchoolBarshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio||Department of Medicine, University of Texas Health Science Center at San AntonioDuke Molecular Physiology Institute, Department of Medicine, Division of Endocrinology, Metabolism and Nutrition, Duke University School of MedicineProgram in Molecular Medicine, University of Massachusetts Chan Medical School
基础医学细胞生物学生物化学
Henriques Felipe,DiMarzio Chloe,Kelly Mark,Hendricks Gregory,Czech Michael P.,Newgard Christopher B.,Wetoska Nicole,Pan Meixia,Reddig Keith,Rowland Leslie A.,Han Xianlin,Ilkayeva Olga R.,Guilherme Adilson.De novo lipogenesis fuels adipocyte autophagosome membrane dynamics[EB/OL].(2025-03-28)[2025-05-05].https://www.biorxiv.org/content/10.1101/2022.05.25.493413.点此复制
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