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Optic atrophy 1 is an A-kinase anchoring protein on lipid droplets that mediates adrenergic control of lipolysis

Abstract : Adrenergic stimulation of adipocytes yields a cAMP signal that activates protein kinase A (PKA). PKA phosphory-lates perilipin, a protein localized on the surface of lipid droplets that serves as a gatekeeper to regulate access of lipases converting stored triglycerides to free fatty acids and glycerol in a phosphorylation-dependent manner. Here, we report a new function for optic atrophy 1 (OPA1), a protein known to regulate mitochondrial dynamics, as a dual-specificity A-kinase anchoring protein associated with lipid droplets. By a variety of protein interaction assays, immunoprecipitation and immunolo-calization experiments, we show that OPA1 organizes a supramolecular complex containing both PKA and perili-pin. Furthermore, by a combination of siRNA-mediated knockdown, reconstitution experiments using full-length OPA1 with or without the ability to bind PKA or truncated OPA1 fused to a lipid droplet targeting domain and cellular delivery of PKA anchoring disruptor peptides, we demonstrate that OPA1 targeting of PKA to lipid droplets is necessary for hormonal control of perilipin phosphoryla-tion and lipolysis.
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https://www.hal.inserm.fr/inserm-02556141
Contributor : Guillaume Pidoux <>
Submitted on : Monday, April 27, 2020 - 6:37:06 PM
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Guillaume Pidoux, Oliwia Witczak, Elisabeth Jarnaess, Linda Myrvold, Henning Urlaub, et al.. Optic atrophy 1 is an A-kinase anchoring protein on lipid droplets that mediates adrenergic control of lipolysis. EMBO Journal, EMBO Press, 2011, 30 (21), pp.4371-4386. ⟨10.1038/emboj.2011.365⟩. ⟨inserm-02556141⟩

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