Mitofusin-2 triggers mitochondria Ca2+ influx from the endoplasmic reticulum to induce apoptosis in hepatocellular carcinoma cells

作者：Wang, Weilin; Xie, Qingsong; Zhou, Xiaohu; Yao, Jingzi; Zhu, Xiaoxiang; Huang, Pengfei; Zhang, Lufei; Wei, Jianfeng; Xie, Haiyang; Zhou, Lin; Zheng, Shusen^*

来源：Cancer Letters, 2015, 358(1): 47-58.

DOI：10.1016/j.canlet.2014.12.025

• Mitochondrial Ca2+ uniporter
• Mitochondrial calcium uptake1
• Mitochondrial calcium uptake 2
• InsP(3)R
• Heparin
• RU360

In previous studies, we confirmed that mitofusin-2 (Mfn2) induced apoptosis in hepatocellular carcinoma (HCC) cells. However, the exact molecular mechanism remained unclear. Mfn2 expressed lower in tumour tissues, compared with adjacent non-cancer tissues. Furthermore, Mfn2 immunostaining was very weak in HCC tissue (P < 0.05) and was significantly associated with tumour size and TNM stage (P = 0.038 and 0.040, respectively), and patients with HCC with lower Mfn2 expression had a poorer prognosis. Overexpression of Mfn2 induced HepG2 cells apoptosis, reduced the mitochondrial membrane potential (Delta Psi m) and endoplasmic reticulum (ER) calcium ion (Ca2+) concentrations, and elevated intracellular reactive oxygen species (ROS) and mitochondrial Ca2+ concentrations. However, when HepG2 cells overexpressing Mfn2 were treated with both heparin and RU360, there was no induction of apoptosis, decline in Delta Psi m or ER Ca2+, or increase in intracellular ROS or mitochondrial Ca2+. We also found downregulation in the expression of mitochondrial calcium uptakel and 2 (MICUl and MICU2) in cells transfected with Adv-Mfn2. Thus, we confirmed that Mfn2 induced apoptosis in HCC cells by triggering influx of Ca2+ into the mitochondria from the ER.

• 出版日期2015-3-1
• 单位浙江大学