The Tnfaip8-PE complex is a novel upstream effector in the anti-autophagic action of insulin

Ji Soo Kim, Jimin Park, Mi Sun Kim, Ji Young Ha, Ye Won Jang, Dong Hae Shin, Jin H. Son

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Defective hepatic autophagy is observed in obesity and diabetes, whereas autophagy is inhibited by insulin in hepatocytes. Insulin-induced anti-autophagy is mediated by non-canonical Gαi3 signaling via an unknown mechanism. Previously, we identified the anti-autophagic activity of Tnfaip8 via activation of mammalian target of rapamycin (mTOR) in the nervous system. Here, we demonstrate that insulin temporally induces Tnfaip8, which mediates the anti-autophagic action of insulin through formation of a novel ternary complex including Tnfaip8, phosphatidylethanolamine (PE) and Gαi3. Specifically, an X-ray crystallographic study of Tnfaip8 from Mus musculus (mTnfaip8) at 2.03 Å together with LC-MS analyses reveals PE in the hydrophobic cavity. However, an mTnfaip8 mutant lacking PE does not interact with Gαi3, indicating that the PE component is critical for the anti-autophagic action of mTnfaip8 via interaction with Gαi3. Therefore, the mTnfaip8-PE complex may act as an essential upstream effector via ternary complex formation most likely with active Gαi3 during insulin-induced anti-autophagy.

Original languageEnglish
Article number6248
JournalScientific Reports
Issue number1
StatePublished - 1 Dec 2017

Bibliographical note

Funding Information:
This work was supported by the grants (2015R1D1A1A01058942 to DHS and 2016R1D1A1A09918309 and 2015M3C7A1028373 to JHS) from the National Research Foundation of Korea (NRF) funded by the Ministry of Education.

Publisher Copyright:
© 2017 The Author(s).


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