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RNA binding protein HuD contributes to β-cell dysfunction by impairing mitochondria dynamicsoa mark
  • Hong, Youlim ;
  • Tak, Hyosun ;
  • Kim, Chongtae ;
  • Kang, Hoin ;
  • Ji, Eunbyul ;
  • Ahn, Sojin ;
  • Jung, Myeongwoo ;
  • Kim, Hong Lim ;
  • Lee, Jeong Hwa ;
  • Kim, Wook ;
  • Lee, Eun Kyung
Citations

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Publication Year
2020-05-01
Journal
Cell Death and Differentiation
Publisher
Springer Nature
Citation
Cell Death and Differentiation, Vol.27 No.5, pp.1633-1643
Mesh Keyword
AnimalsCell LineDiabetes Mellitus, ExperimentalELAV-Like Protein 4Gene Expression RegulationGTP PhosphohydrolasesInsulin-Secreting CellsMice, KnockoutMitochondriaMitochondrial DynamicsProtein BindingRNA, Messenger
All Science Classification Codes (ASJC)
Molecular BiologyCell Biology
Abstract
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.
ISSN
1476-5403
Language
eng
URI
https://aurora.ajou.ac.kr/handle/2018.oak/30998
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85074630447&origin=inward
DOI
https://doi.org/10.1038/s41418-019-0447-x
Journal URL
http://www.nature.com/cdd/index.html
Type
Article
Funding
Acknowledgements This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (2017R1A2B2009381, 2017R1A2B2005508, and 2019M3E5D5066526).
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