Mitochondrial Dysfunction and Adipogenic Reduction by Prohibitin Silencing in 3T3-L1 Cells

• Type of Material: Article
• Authors: Dong Liu, Morehouse School of Medicine; Yiming Lin, Emory University; Ting Kang, Morehouse School of Medicine; Bo Huang, Morehouse School of Medicine; Wei Xu, Morehouse School of Medicine; Minerva Garcia-Barrio, Morehouse School of Medicine; Moshood Olatinwo, Morehouse School of Medicine; Roland Matthews, Morehouse School of Medicine; Y. Eugene Chen, University of Michigan; Winston E. Thompson, Morehouse School of Medicine
• Language: English
• Date: 2012-03-30
• Publisher: Public Library Science
• Publication Version: Final Published Version
• Copyright Statement: © 2012 Liu et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0034315
• Title of Journal or Parent Work: PLoS ONE
• Volume: 7
• Issue: 3
• Start Page: e34315
• End Page: e34315
• Grant/Funding Information: and by the Department of Defense grant BC020050 to WET; This study was supported by the National Institutes of Health grants G12RR003034 and G12RR003034-supplement to DL, U54HD41749 to WET
• Keywords: Adipose tissue; Proteins; Cristae morphogenesis; C-MYC; Science & Technology; Science & Technology - Other Topics; Membrane; DNA nucleoids; Activation; Cancer cells; Multidisciplinary Sciences; Gene expression; Adipocyte differentiation
• Research Categories: Biology, Physiology; Biology, Genetics; Health Sciences, Obstetrics and Gynecology; Health Sciences, Oncology; Biology, Cell

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.