Atg8 licenses adipokine nuclear exit

Poling, M. E.; Sullivan, C. E.; Brent, A. E.; Hafer, T. L.; Rajan, A.

doi:10.1101/2021.01.29.428913

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bioRxiv · 10.1101/2021.01.29.428913

Atg8 licenses adipokine nuclear exit

Poling, M. E.·Sullivan, C. E.·Brent, A. E.·Hafer, T. L.·Rajan, A.

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Abstract

Adipokines released from the adipocytes function as a systemic adipometer; they impinge on neural circuits to signal nutrient status. On starvation, adipokines must be retained to signal energy deficit; else, it significantly reduces starvation survival. But how fat cells retain adipokines is unclear. Here, we demonstrate that Atg8, a cell-intrinsic autophagy factor, regulates the starvation-induced acute retention of the Leptin Drosophila ortholog Upd2. We show that on starvation, as a direct consequence of Atg8s lipidation, Upd2 accumulates in the nucleus. We illustrate that Upd2s nuclear retention is critical to fat mobilization and increased starvation resilience. Furthermore, nuclear Upd2 promotes the expression of a secreted innate immune gene signature. This hints at an unanticipated connection between adipokine nuclear retention and increased innate immunity. In conclusion, we propose that, during starvation, Atg8s role is not just limited to autophagy but is critical for withholding adipokines in the nucleus to promote starvation resilience. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=178 HEIGHT=200 SRC="FIGDIR/small/428913v5_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@1826425org.highwire.dtl.DTLVardef@17cca52org.highwire.dtl.DTLVardef@1c70ac7org.highwire.dtl.DTLVardef@94a024_HPS_FORMAT_FIGEXP M_FIG C_FIG O_LIIn fed state Upd2 requires Atg8 for nuclear exit and cytosolic localization. C_LIO_LIAtg8s lipidation on starvation results in Upd2s nuclear accumulation. C_LIO_LIUpd2 nuclear retention on starvation increases fat mobilization and post-starvation hunger. C_LIO_LIOn starvation Upd2 nuclear retention increases expression of a secreted innate immune signature. C_LI

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Poling, M. E., Sullivan, C. E., Brent, A. E., Hafer, T. L., Rajan, A.. 2021-01-31. Atg8 licenses adipokine nuclear exit. https://doi.org/10.1101/2021.01.29.428913

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