title: Downregulation of OPA3 is responsible for transforming growth factor-β-induced mitochondrial elongation and F-actin rearrangement in retinal pigment epithelial ARPE-19 cells.
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.
authors: Department of Bio and Brain Engineering, KAIST, Daejeon, Korea. ryus@kaist.ac.kr
authors: Seung-Wook
authors: SW
authors: Ryu
authors: Jonghee
authors: J
authors: Yoon
authors: Nambin
authors: N
authors: Yim
authors: Kyungsun
authors: K
authors: Choi
authors: Chulhee
authors: C
authors: Choi
mesh_terms: D000199:Actins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D034281:Dynamins; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects; D033681:Mitochondrial Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D053140:Organelle Shape / Q000187:drug effects; D011506:Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction; D051899:Smad2 Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014746:Vimentin / Q000819:agonists / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D015703:Antigens, CD; C050361:CDH2 protein, human; D015820:Cadherins; D008869:Microtubule-Associated Proteins; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; C443108:OPA3 protein, human; D011506:Proteins; D034741:RNA, Small Interfering; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D016212:Transforming Growth Factor beta; D014746:Vimentin; D020558:GTP Phosphohydrolases; C470017:Mfn1 protein, human; C110768:DNM1L protein, human; D034281:Dynamins
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