Description:
<jats:title>Abstract</jats:title>
<jats:p>Invadolysin is a novel metalloprotease conserved amongst metazoans that is essential for life in <jats:italic>Drosophila</jats:italic>. We previously showed that invadolysin was essential for the cell cycle and cell migration, linking to metabolism through a role in lipid storage and interaction with mitochondrial proteins. In this study we demonstrate that <jats:italic>invadolysin</jats:italic> mutants exhibit increased autophagy and decreased glycogen storage – suggestive of a role for invadolysin in insulin signaling in <jats:italic>Drosophila</jats:italic>. Consistent with this, effectors of insulin signaling were decreased in <jats:italic>invadolysin</jats:italic> mutants. In addition, we discovered that invadolysin was deposited on newly synthesized lipid droplets in a PKC-dependent manner. We examined two <jats:italic>in vitro</jats:italic> models of adipogenesis for the expression and localization of invadolysin. The level of invadolysin increased during both murine 3T3-L1 and human Simpson-Golabi-Behmel syndrome (SGBS), adipogenesis. Invadolysin displayed a dynamic localization to lipid droplets over the course of adipogenesis, which may be due to the differential expression of distinct invadolysin variants. Pharmacological inhibition of adipogenesis abrogated the increase in invadolysin. In summary, our results on <jats:italic>in vivo</jats:italic> and <jats:italic>in vitro</jats:italic> systems highlight an important role for invadolysin in insulin signaling and adipogenesis.</jats:p>