Mitochondrial calcium uniporter （MCU） is a conserved Ca2＋ transporter at mitochondrial in eukaryotic cells. However, the role of MCU protein in oxidative stress- induced cell death remains unclear. Here, we showed ...Mitochondrial calcium uniporter （MCU） is a conserved Ca2＋ transporter at mitochondrial in eukaryotic cells. However, the role of MCU protein in oxidative stress- induced cell death remains unclear. Here, we showed that ectopically expressed MCU is mitochondrial local- ized in both HeLa and primary cerebellar granule neu- rons （CGNs）. Knockdown of endogenous MCU decreases mitochondrial Ca2＋ uptake following his- tamine stimulation and attenuates cell death induced by oxidative stress in both HeLa cells and CGNs. We also found MCU interacts with VDACl and mediates VDAC1 overexpression-induced cell death in CGNs. This finding demonstrates that MCU-VDACl complex regulates mi- tochondrial Ca2＋ uptake and oxidative stress-induced apoptosis, which might represent therapeutic targets for oxidative stress related diseases.展开更多
基金This work was supported by a grant from Beijing Nature Science Foundation （Grant No. 7132147）. We sincerely thank Professor Guangju Ji for kindly providing plasmid Mito-GCaMP3 for us.
文摘Mitochondrial calcium uniporter （MCU） is a conserved Ca2＋ transporter at mitochondrial in eukaryotic cells. However, the role of MCU protein in oxidative stress- induced cell death remains unclear. Here, we showed that ectopically expressed MCU is mitochondrial local- ized in both HeLa and primary cerebellar granule neu- rons （CGNs）. Knockdown of endogenous MCU decreases mitochondrial Ca2＋ uptake following his- tamine stimulation and attenuates cell death induced by oxidative stress in both HeLa cells and CGNs. We also found MCU interacts with VDACl and mediates VDAC1 overexpression-induced cell death in CGNs. This finding demonstrates that MCU-VDACl complex regulates mi- tochondrial Ca2＋ uptake and oxidative stress-induced apoptosis, which might represent therapeutic targets for oxidative stress related diseases.
