A genetic interaction map of insulin production identifies Mfi as an inhibitor of mitochondrial fission.

Publication Type:


Endocrinology (2018)


<p>Insulin production by the pancreatic beta cell is critical for the glucose homeostasis of the whole organism. While transcription factors required for insulin production are known, the upstream pathways that control insulin production are less clear. To further elucidate this regulatory network, we created a genetic interaction map of insulin production by performing ∼20,000 pairwise RNA interference (RNAi) knockdowns of insulin promoter regulators. Our map correctly predicted known physical complexes in the electron transport chain as well as a role for Spry2 in the unfolded protein response. To further validate our map, we used it to predict the function of an unannotated gene encoding a 37 kDa protein with no identifiable domains we have termed Mfi (Mff-interactor). We show that Mfi is a novel binding partner of the mitochondrial fission factor (Mff) and that Mfi inhibits dynamin-like protein 1 (Drp1) recruitment to mitochondria. Our data provide a novel resource to understand the regulatory network of insulin promoter activity.</p>