title: Mitochondrial calcium uniporter protein MCU is involved in oxidative stress-induced cell death.
abstract: Mitochondrial calcium uniporter (MCU) is a conserved Ca(2+) 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 localized in both HeLa and primary cerebellar granule neurons (CGNs). Knockdown of endogenous MCU decreases mitochondrial Ca(2+) uptake following histamine stimulation and attenuates cell death induced by oxidative stress in both HeLa cells and CGNs. We also found MCU interacts with VDAC1 and mediates VDAC1 overexpression-induced cell death in CGNs. This finding demonstrates that MCU-VDAC1 complex regulates mitochondrial Ca(2+) uptake and oxidative stress-induced apoptosis, which might represent therapeutic targets for oxidative stress related diseases.
authors.affiliation: State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Yajin
authors.initials: Y
authors.lastname: Liao
authors.forename: Yumin
authors.initials: Y
authors.lastname: Hao
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.forename: Qing
authors.initials: Q
authors.lastname: He
authors.forename: Zengqiang
authors.initials: Z
authors.lastname: Yuan
authors.forename: Jinbo
authors.initials: J
authors.lastname: Cheng
mesh_terms: D000818:Animals; D017209:Apoptosis; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D002531:Cerebellum / Q000166:cytology; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D018384:Oxidative Stress; D050994:Voltage-Dependent Anion Channels / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D050994:Voltage-Dependent Anion Channels; C034703:mitochondrial calcium uniporter; D002118:Calcium