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PLoS One. 2013 May 3;8(5):e63495. doi: 10.1371/journal.pone.0063495. Print 2013.

Downregulation of OPA3 is responsible for transforming growth factor-β-induced mitochondrial elongation and F-actin rearrangement in retinal pigment epithelial ARPE-19 cells.

Author information

1
Department of Bio and Brain Engineering, KAIST, Daejeon, Korea. ryus@kaist.ac.kr

Abstract

Transforming growth factor-β signaling is known to be a key signaling pathway in the induction of epithelial-mesenchymal transition. However, the mechanism of TGF-β signaling in the modulation of EMT remains unclear. In this study, we found that TGF-β treatment resulted in elongation of mitochondria accompanied by induction of N-cadherin, vimentin, and F-actin in retinal pigment epithelial cells. Moreover, OPA3, which plays a crucial role in mitochondrial dynamics, was downregulated following TGF-β treatment. Suppression of TGF-β signaling using Smad2 siRNA prevented loss of OPA3 induced by TGF-β. Knockdown of OPA3 by siRNA and inducible shRNA significantly increased stress fiber levels, cell length, cell migration and mitochondrial elongation. In contrast, forced expression of OPA3 in ARPE-19 cells inhibited F-actin rearrangement and induced mitochondrial fragmentation. We also showed that Drp1 depletion increased cell length and induced rearrangement of F-actin. Depletion of Mfn1 blocked the increase in cell length during TGF-β-mediated EMT. These results collectively substantiate the involvement of mitochondrial dynamics in TGF-β-induced EMT.

PMID:
23658835
PMCID:
PMC3643898
DOI:
10.1371/journal.pone.0063495
[Indexed for MEDLINE]
Free PMC Article

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