Close 2020 Cells

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Publications in the MiPMap
Close AF, Dadheech N, Lemieux H, Wang Q, Buteau J (2020) Disruption of beta-cell mitochondrial networks by the orphan nuclear receptor Nor1/Nr4a3. Cells 9:E168.

» PMID: 31936632 Open Access

Close AF, Dadheech N, Lemieux H, Wang Q, Buteau J (2020) Cells

Abstract: Nor1, the third member of the Nr4a subfamily of nuclear receptor, is garnering increased interest in view of its role in the regulation of glucose homeostasis. Our previous study highlighted a proapoptotic role of Nor1 in pancreatic beta cells and showed that Nor1 expression was increased in islets isolated from type 2 diabetic individuals, suggesting that Nor1 could mediate the deterioration of islet function in type 2 diabetes. However, the mechanism remains incompletely understood. We herein investigated the subcellular localization of Nor1 in INS832/13 cells and dispersed human beta cells. We also examined the consequences of Nor1 overexpression on mitochondrial function and morphology. Our results show that, surprisingly, Nor1 is mostly cytoplasmic in beta cells and undergoes mitochondrial translocation upon activation by proinflammatory cytokines. Mitochondrial localization of Nor1 reduced glucose oxidation, lowered ATP production rates, and inhibited glucose-stimulated insulin secretion. Western blot and microscopy images revealed that Nor1 could provoke mitochondrial fragmentation via mitophagy. Our study unveils a new mode of action for Nor1, which affects beta-cell viability and function by disrupting mitochondrial networks.

Keywords: Nr4a, Apoptosis, Cytokines, Diabetes, Mitochondria, Mitophagy, Nuclear receptor Bioblast editor: Plangger M O2k-Network Lab: CA Edmonton Lemieux H


Labels: MiParea: Respiration, nDNA;cell genetics, Genetic knockout;overexpression  Pathology: Diabetes 

Organism: Rat  Tissue;cell: Islet cell;pancreas;thymus  Preparation: Permeabilized cells, Intact cells 


Coupling state: LEAK, ROUTINE  Pathway: N, S, CIV, NS, ROX  HRR: Oxygraph-2k 

Labels, 2020-01