Cell death and differentiation, 2020-05, Vol.27 (5), p.1633-1643
2020
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- Autor(en) / Beteiligte
- Titel
- RNA binding protein HuD contributes to β-cell dysfunction by impairing mitochondria dynamics
- Ist Teil von
- Cell death and differentiation, 2020-05, Vol.27 (5), p.1633-1643
- Ort / Verlag
- London: Nature Publishing Group UK
- Erscheinungsjahr
- 2020
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Imbalanced mitochondrial dynamics in pancreatic β-cells contributes to β-cell dysfunction in diabetes; however, the molecular mechanisms underlying mitochondrial dynamics in the pathology of diabetes are not fully elucidated. We previously reported the reduction of RNA binding protein HuD in pancreatic β-cells of diabetes. Herein, we demonstrate that HuD plays a novel role in the regulation of mitochondrial dynamics by promoting mitochondrial fusion. We show enhanced mitochondrial fragmentation in the pancreas of db / db mice and HuD KO mice. Downregulation of HuD increases the number of cells with fragmented mitochondria and reduces the mitochondrial activity determined by mitochondrial membrane potential and ATP production in mouse insulinoma βTC6 cells. HuD binds to 3′-untraslated region of mitofusin 2 ( Mfn2 ) mRNA and positively regulates its expression. Ectopic expression of Mfn2 in βTC6 cells stably expressing short hairpin RNA against HuD (shHuD) restores HuD-mediated mitochondrial dysfunction. Taken together, our results suggest that HuD regulates mitochondrial dynamics by regulating Mfn2 level and its reduced expression leads to mitochondrial dysfunction in pancreatic β-cells.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1350-9047, 1476-5403eISSN: 1476-5403DOI: 10.1038/s41418-019-0447-xTitel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7206106
- Format
- –
- Schlagworte
- 13/89, 14/1, 14/34, 14/63, 45/90, 631/45/500, 64/60, 692/699/317, 82/80, 96/109, Animals, Apoptosis, Beta cells, Biochemistry, Biomedical and Life Sciences, Cell Biology, Cell Cycle Analysis, Cell Line, Diabetes, Diabetes mellitus, Diabetes Mellitus, Experimental - genetics, Diabetes Mellitus, Experimental - pathology, Ectopic expression, ELAV-Like Protein 4 - metabolism, Gene Expression Regulation, GTP Phosphohydrolases - genetics, GTP Phosphohydrolases - metabolism, Insulin-Secreting Cells - metabolism, Insulin-Secreting Cells - pathology, Insulinoma, Life Sciences, Membrane potential, Mice, Knockout, Mitochondria, Mitochondria - metabolism, Mitochondria - ultrastructure, Mitochondrial Dynamics - genetics, Molecular modelling, mRNA, Pancreas, Protein Binding, RNA, Messenger - genetics, RNA, Messenger - metabolism, RNA-binding protein, Stem Cells