%0 Journal Article
%T Downregulation of OPA3 Is Responsible for Transforming Growth Factor-¦Â-Induced Mitochondrial Elongation and F-Actin Rearrangement in Retinal Pigment Epithelial ARPE-19 Cells
%A Seung-Wook Ryu
%A Jonghee Yoon
%A Nambin Yim
%A Kyungsun Choi
%A Chulhee Choi
%J PLOS ONE
%D 2013
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0063495
%X Transforming growth factor-¦Â signaling is known to be a key signaling pathway in the induction of epithelial¨Cmesenchymal transition. However, the mechanism of TGF-¦Â signaling in the modulation of EMT remains unclear. In this study, we found that TGF-¦Â 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-¦Â treatment. Suppression of TGF-¦Â signaling using Smad2 siRNA prevented loss of OPA3 induced by TGF-¦Â. 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-¦Â-mediated EMT. These results collectively substantiate the involvement of mitochondrial dynamics in TGF-¦Â-induced EMT.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0063495