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Endocrinology. 2018 Sep 1;159(9):3321-3330. doi: 10.1210/en.2018-00426.

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

Author information

1
Diabetes Center, University of California, San Francisco, San Francisco, California.
2
Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, California.
3
Small Molecules Discovery Center, University of California, San Francisco, San Francisco, California.
4
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, California.
5
Division of Endocrinology and Metabolism, Department of Medicine, University of California San Francisco, San Francisco, California.

Abstract

Insulin production by the pancreatic β 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 ∼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.

PMID:
30059978
PMCID:
PMC6112596
[Available on 2019-09-01]
DOI:
10.1210/en.2018-00426

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