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Histone deacetylase inhibitors induce mitochondrial elongation

Lee, JS; Yoon, YG; Yoo, SH; Jeong, NY; Jeong, SH; Lee, SY; Jung, DI; Jeong, SY; Yoo, YH
Journal of cellular physiology, 227(7):2856-2869, 2012
Journal Title
Journal of cellular physiology
Although various stimuli-inducing cell demise are known to alter mitochondrial morphology, it is currently debated whether alteration of mitochondrial morphology is per se responsible for apoptosis execution or prevention. This study was undertaken to examine the effect of histone deacetylase (HDAC) inhibitors on mitochondrial fusion-fission equilibrium. The mechanism underlying HDAC inhibitor-induced alteration of mitochondrial morphology was examined in various cells including primary cultured cells and untransformed and cancer cell lines treated with seven different HDAC inhibitors. Suberoylanilide hydroxamic acid (SAHA)-induced mitochondrial elongation in both Hep3B and Bcl-2-overexpressing Hep3B cells, apart from its apoptosis induction function. SAHA significantly decreased the expression of mitochondrial fission protein Fis1 and reduced the translocation of Drp1 to the mitochondria. Fis1 overexpression attenuated SAHA-induced mitochondrial elongation. In addition, depletion of mitochondrial fusion proteins, Mfn1 or Opa1, by RNA interference also attenuated SAHA-induced mitochondrial elongation. All of the HDAC inhibitors we examined induced mitochondrial elongation in all the cell types tested at both subtoxic and toxic concentrations. These results indicate that HDAC inhibitors induce mitochondrial elongation, irrespective of the induction of apoptosis, which may be linked to alterations of mitochondrial dynamics regulated by mitochondrial morphology-regulating proteins. Since mitochondria have recently emerged as attractive targets for cancer therapy, our findings that HDAC inhibitors altered mitochondrial morphology may support the rationale for these agents as novel therapeutic approaches against cancer. Further, the present study may provide insight into a valuable experimental strategy for simple manipulation of mitochondrial morphology.
MeSH terms
Acetylation/drug effectsAntineoplastic Agents/pharmacologyApoptosis/drug effects/geneticsCell Division/drug effects/geneticsCell LineCell Line, TumorGTP Phosphohydrolases/genetics/metabolismHistone Deacetylase Inhibitors/*pharmacologyHistones/physiologyHumansHydroxamic Acids/pharmacologyMembrane Fusion/drug effects/geneticsMembrane Proteins/genetics/metabolismMicrotubule-Associated Proteins/genetics/metabolismMitochondria/*drug effects/enzymology/*physiologyMitochondrial Membrane Transport Proteins/metabolismMitochondrial Proteins/genetics/metabolism
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Journal Papers > School of Medicine / Graduate School of Medicine > Medical Genetics
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정, 선용
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