Model for labile iron-induced ferroptosis. (IMAGE)
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8HQ/FAC treatment increases the intercellular labile iron; labile iron induces Mitochondrial ROS production and increases membrane permeability that results in Ca2+ influx. Excessive Ca2+ in cytoplasm activates calpain-1 and results in rearrangement of cytoskeleton. Meanwhile, excessive Ca2+ uptake of mitochondrion leads to mitochondrial swelling and large bubbles blowing from the plasma, which exhibits the feature of oncotic cell death. While, the nucleus undergoes pycnosis and chromatin condensation, which exhibits the feature of apoptosis. The inhibitor of mitochondrial calcium uniporter (MCU), such as DS16570511 and MCU-i4, can inhibit Ca2+ uptake of mitochondria and prevent the ferroptosis induced by labile iron.
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