Cardiovascular Research Institute, Morehouse School of Medicine, Atlanta, Georgia, United States of America.
PLoS One. 2012;7(3):e34315. doi: 10.1371/journal.pone.0034315. Epub 2012 Mar 30.
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.
线粒体生物发生的增加已被证明伴随着棕色和白色脂肪细胞的分化。抑制素（PHBs）由两种进化上保守的蛋白质组成，即抑制素-1（PHB1）和抑制素-2（PHB2），存在于线粒体内膜的高分子量复合物中。然而，关于线粒体 PHBs 在脂肪生成中的作用知之甚少。在本研究中，我们证明了 PHB1 和 PHB2 的水平在 3T3-L1 前脂肪细胞的脂肪生成过程中显著增加，尤其是在线粒体中。寡核苷酸 siRNA 敲低 PHB1 或 PHB2 显著降低了脂肪生成标志物的表达、脂质的积累和细胞外信号调节激酶的磷酸化。此外，在 3T3-L1 细胞中沉默 PHB 时观察到线粒体网的碎片化、线粒体嵴的丧失、线粒体含量的减少、线粒体复合物 I 活性的损害以及 ROS 的过度产生。我们的结果表明，PHBs 是促进 3T3-L1 脂肪细胞分化的关键介质，可能是肥胖症治疗的潜在靶点。
