期刊
FASEB JOURNAL
卷 21, 期 10, 页码 2474-2485出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.06-7345com
关键词
HCV core; mitochondria; cytosolic Ca2+; MAVS
资金
- NIAAA NIH HHS [AA12863] Funding Source: Medline
Many viruses have evolved mechanisms to alter mitochondrial function. The hepatitis C virus (HCV) produces a viral core protein that targets to mitochondria and increases Ca2(+)- dependent ROS production. The aim of this study was to determine whether core's effects are mediated by changes in mitochondrial Ca2+ uptake. Core expression caused enhanced mitochondrial Ca2+ uptake in response to ER Ca2+ release induced by thapsigargin or ATP. It also increased mitochondrial superoxide production and mitochondrial permeability transition ( MPT). Incubating mouse liver mitochondria with an HCV core ( 100 ng/mg) in vitro increased Ca2+ entry rate by similar to 2-fold. Entry was entirely inhibited by the mitochondrial Ca2+ uniporter inhibitor, Ru-360, but not influenced by an Na+/ Ca2+ exchanger inhibitor or ROS scavengers. These results indicate that core directly increases mitochondrial Ca2+ uptake via a primary effect on the uniporter. This enhanced the ability of mitochondria to sequester Ca2+ in response to ER Ca2+ release, and increased mitochondrial ROS production and MPT. Thus, the mitochondrial Ca2+ uniporter is a newly identified target for viral modification of cell function.
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