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Publication : A Genetic Interaction Map of Insulin Production Identifies Mfi as an Inhibitor of Mitochondrial Fission.

First Author  Lee J Year  2018
Journal  Endocrinology Volume  159
Issue  9 Pages  3321-3330
PubMed ID  30059978 Mgi Jnum  J:286525
Mgi Id  MGI:6200588 Doi  10.1210/en.2018-00426
Citation  Lee J, et al. (2018) A Genetic Interaction Map of Insulin Production Identifies Mfi as an Inhibitor of Mitochondrial Fission. Endocrinology 159(9):3321-3330
abstractText  Insulin production by the pancreatic beta cell is critical for the glucose homeostasis of the whole organism. Although the 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 approximately 20,000 pairwise RNA interference knockdowns of insulin promoter regulators. Our map correctly predicted known physical complexes in the electron transport chain and 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 mitochondrial fission factor interactor (Mfi). We have shown that Mfi is a binding partner of the mitochondrial fission factor and that Mfi inhibits dynamin-like protein 1 recruitment to mitochondria. Our data provide a resource to understand the regulatory network of insulin promoter activity.
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