Travaglione Sara, Loizzo Stefano, Rizza Teresa, Del Brocco Antonella, Ballan Giulia, Guidotti Marco, Vona Rosa, Di Nottia Michela, Torraco Alessandra, Carrozzo Rosalba, Fiorentini Carla, Fabbri Alessia
Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy.
FEBS J. 2014 Aug;281(15):3473-88. doi: 10.1111/febs.12874. Epub 2014 Jul 1.
Mitochondria are dynamic organelles that constantly change shape and structure in response to different stimuli and metabolic demands of the cell. The Escherichia coli protein toxin cytotoxic necrotizing factor 1 (CNF1) has recently been reported to influence mitochondrial activity in a mouse model of Rett syndrome and to increase ATP content in the brain tissue of an Alzheimer's disease mouse model. In the present work, the ability of CNF1 to influence mitochondrial activity was investigated in IEC-6 normal intestinal crypt cells. In these cells, the toxin was able to induce an increase in cellular ATP content, probably due to an increment of the mitochondrial electron transport chain. In addition, the CNF1-induced Rho GTPase activity also caused changes in the mitochondrial architecture that mainly consisted in the formation of a complex network of elongated mitochondria. The involvement of the cAMP-dependent protein kinase A signaling pathway was postulated. Our results demonstrate that CNF1 positively affects mitochondria by bursting their energetic function and modifying their morphology.
线粒体是动态细胞器，会根据细胞的不同刺激和代谢需求不断改变形状和结构。最近有报道称，大肠杆菌蛋白毒素细胞毒性坏死因子1（CNF1）在雷特综合征小鼠模型中会影响线粒体活性，并增加阿尔茨海默病小鼠模型脑组织中的ATP含量。在本研究中，我们在IEC-6正常肠隐窝细胞中研究了CNF1影响线粒体活性的能力。在这些细胞中，毒素能够诱导细胞ATP含量增加，这可能是由于线粒体电子传递链增加所致。此外，CNF1诱导的Rho GTPase活性还导致线粒体结构发生变化，主要表现为形成复杂的细长线粒体网络。推测cAMP依赖性蛋白激酶A信号通路参与其中。我们的结果表明，CNF1通过增强线粒体的能量功能和改变其形态来对线粒体产生积极影响。
