A Genetic Interaction Map of Insulin Production Identifies Mfi as an Inhibitor of Mitochondrial Fission
| Autor: | Thomas G. Hennings, Deeksha Gambhir Chopra, Kenny K. H. Ang, Gregory M. Ku, Michael S. German, Ian W. Vaughn, Justin J Choe, Michelle R. Arkin, Christopher Lan, Michael T. McManus, Jessica M. Lee, Zachary Pappalardo, Steven Chen |
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| Rok vydání: | 2018 |
| Předmět: |
Dynamins
0301 basic medicine medicine.medical_specialty Mitochondrial fission factor medicine.medical_treatment Gene regulatory network Mitochondrion Mitochondrial Dynamics Cell Line GTP Phosphohydrolases Mitochondrial Proteins Mice 03 medical and health sciences Endocrinology Insulin-Secreting Cells Internal medicine medicine Animals Humans Insulin Glucose homeostasis Gene Regulatory Networks Promoter Regions Genetic Transcription factor Technical Resource Chemistry Intracellular Signaling Peptides and Proteins Membrane Proteins Mitochondria Cell biology 030104 developmental biology Unfolded Protein Response Unfolded protein response Mitochondrial fission Microtubule-Associated Proteins |
| Zdroj: | Endocrinology. 159:3321-3330 |
| ISSN: | 1945-7170 |
| DOI: | 10.1210/en.2018-00426 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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