title: Mitochondrial dysfunction and adipogenic reduction by prohibitin silencing in 3T3-L1 cells.
abstract: Increase in mitochondrial biogenesis has been shown to accompany brown and white adipose cell differentiation. Prohibitins (PHBs), comprised of two evolutionarily conserved proteins, prohibitin-1 (PHB1) and prohibitin-2 (PHB2), are present in a high molecular-weight complex in the inner membrane of mitochondria. However, little is known about the effect of mitochondrial PHBs in adipogenesis. In the present study, we demonstrate that the levels of both PHB1 and PHB2 are significantly increased during adipogenesis of 3T3-L1 preadipocytes, especially in mitochondria. Knockdown of PHB1 or PHB2 by oligonucleotide siRNA significantly reduced the expression of adipogenic markers, the accumulation of lipids and the phosphorylation of extracellular signal-regulated kinases. In addition, fragmentation of mitochondrial reticulum, loss of mitochondrial cristae, reduction of mitochondrial content, impairment of mitochondrial complex I activity and excessive production of ROS were observed upon PHB-silencing in 3T3-L1 cells. Our results suggest that PHBs are critical mediators in promoting 3T3-L1 adipocyte differentiation and may be the potential targets for obesity therapies.
authors.affiliation: Cardiovascular Research Institute, Morehouse School of Medicine, Atlanta, Georgia, United States of America. dliu@msm.edu
authors.forename: Dong
authors.initials: D
authors.lastname: Liu
authors.forename: Yiming
authors.initials: Y
authors.lastname: Lin
authors.forename: Ting
authors.initials: T
authors.lastname: Kang
authors.forename: Bo
authors.initials: B
authors.lastname: Huang
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Minerva
authors.initials: M
authors.lastname: Garcia-Barrio
authors.forename: Moshood
authors.initials: M
authors.lastname: Olatinwo
authors.forename: Roland
authors.initials: R
authors.lastname: Matthews
authors.forename: Y Eugene
authors.initials: YE
authors.lastname: Chen
authors.forename: Winston E
authors.initials: WE
authors.lastname: Thompson
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology*; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D004272:DNA, Mitochondrial / Q000378:metabolism; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D051379:Mice; D018613:Microscopy, Confocal / Q000379:methods; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008928:Mitochondria / Q000378:metabolism*; D009841:Oligonucleotides / Q000235:genetics; D000091402:Prohibitins; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D004272:DNA, Mitochondrial; D009841:Oligonucleotides; C000717328:PHB protein, human; C000717331:PHB2 protein, human; C000717333:Phb2 protein, mouse; D000091402:Prohibitins; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D012097:Repressor Proteins