Mobilization of Ca2+ from endoplasmic reticulum to mitochondria plays a positive role in the early stage of UV- or TNFalpha-induced apoptosis.
Previously it was known that cytosolic Ca(2+) elevation was involved in regulating UV- or TNFalpha-induced apoptosis. Here, we reported new evidence that mitochondrial Ca(2+) signal is also involved in the apoptotic process. First, using living cell imaging techniques, we observed multiple mitochondrial Ca(2+) spikes during the early stage of UV- or TNFalpha-induced apoptosis. Second, the mitochondrial Ca(2+) spikes were synchronous with cytosolic Ca(2+) spikes observed in apoptosis, which preceded cytochrome c (cyt-c) release. Third, blocking the mitochondrial Ca(2+) elevation by applying a mitochondrial uniporter inhibitor could suppress UV-induced apoptosis in HeLa cells. Finally, overexpressing an anti-apoptotic protein, Bcl-2, could suppress the mitochondrial Ca(2+) elevation. Furthermore, it appeared that the elevation of mitochondrial Ca(2+) during apoptosis was caused by a direct coupling between endoplasmic reticulum (ER) and mitochondria through IP(3) receptors. Taken together, these findings suggest that Ca(2+) mobilization from ER to mitochondria can play a significant role in the apoptotic signaling pathway.
Lao
Yuanzhi
Y
Department of Biology, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
Chang
Donald C
DC
D017209:Apoptosis; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002413:Cations, Divalent / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D017136:Ion Transport; D008928:Mitochondria / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014466:Ultraviolet Rays
D002413:Cations, Divalent; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D002118:Calcium