Unit of Experimental Biology and Genetics, Department of Clinical and Experimental Medicine, University of Pisa, Via Volta 4, 56126, Pisa, Italy.
Stem Cell Rev Rep. 2014 Dec;10(6):871-87. doi: 10.1007/s12015-014-9540-1.
Prohibitins are pleiotropic proteins, whose multiple roles are emerging as key elements in the regulation of cell survival and proliferation. Indeed, prohibitins interact with several intracellular proteins strategically involved in the regulation of cell cycle progression in response to extracellular growth signals. Prohibitins also have regulatory functions in mitochondrial fusion and cristae morphogenesis, phenomena related to the ability of self-renewing embryonic stem cells to undergo differentiation, during which mitochondria develop numerous cristae, increase in number, and generate an extensive reticular network. We recently identified a Prohibitin 2 homolog (DjPhb2) that is expressed in adult stem cells (neoblasts) of planarians, a well-known model system for in vivo studies on stem cells and tissue regeneration. Here, we show that in DjPhb2 silenced planarians, most proliferating cells disappear, with the exception of a subpopulation of neoblasts localized along the dorsal body midline. Neoblast depletion impairs regeneration and, finally, leads animals to death. Our in vivo findings demonstrate that prohibitin 2 plays an important role in regulating stem cell biology, being involved in both the control of cell cycle progression and mitochondrial cristae morphogenesis.
抑素是一种多功能蛋白，其多种作用正逐渐成为细胞存活和增殖调控的关键因素。事实上，抑素与几种细胞内蛋白相互作用，这些蛋白在响应细胞外生长信号时，参与调控细胞周期进程中具有战略意义。抑素在线粒体融合和嵴形态发生中也具有调节功能，这些现象与自我更新的胚胎干细胞进行分化的能力有关，在此过程中线粒体形成大量嵴，数量增加，并产生广泛的网状结构。我们最近在扁形动物的成年干细胞（neoblasts）中鉴定出一种抑素 2 同源物（DjPhb2），扁形动物是用于干细胞和组织再生的体内研究的知名模型系统。在这里，我们表明在 DjPhb2 沉默的扁形动物中，大多数增殖细胞消失，除了沿身体中线背部定位的一小部分 neoblasts 亚群。neoblasts 的耗竭会损害再生，最终导致动物死亡。我们的体内发现表明，抑素 2 在调节干细胞生物学方面发挥着重要作用，参与细胞周期进程的控制和线粒体嵴形态发生。
