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Mitofusin-2 triggers mitochondria Ca2+ influx from the endoplasmic reticulum to induce apoptosis in hepatocellular carcinoma cells.
- Source :
-
Cancer Letters . Mar2015, Vol. 358 Issue 1, p47-58. 12p. - Publication Year :
- 2015
-
Abstract
- 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 (ΔΨm) and endoplasmic reticulum (ER) calcium ion (Ca 2+ ) concentrations, and elevated intracellular reactive oxygen species (ROS) and mitochondrial Ca 2+ concentrations. However, when HepG2 cells overexpressing Mfn2 were treated with both heparin and RU360, there was no induction of apoptosis, decline in ΔΨm or ER Ca 2+ , or increase in intracellular ROS or mitochondrial Ca 2+ . We also found downregulation in the expression of mitochondrial calcium uptake1 and 2 (MICU1 and MICU2) in cells transfected with Adv-Mfn2. Thus, we confirmed that Mfn2 induced apoptosis in HCC cells by triggering influx of Ca 2+ into the mitochondria from the ER. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03043835
- Volume :
- 358
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Cancer Letters
- Publication Type :
- Academic Journal
- Accession number :
- 100561838
- Full Text :
- https://doi.org/10.1016/j.canlet.2014.12.025