5-Lipoxygenase-mediated mitochondrial damage and apoptosis of mononuclear cells in ESRD patients.
Recently, it was demonstrated that IRE1-extended ROS production stimulated caspase-2-Bid-mediated mitochondrial damage which activated the inflammasome [16].
However, measuring ROS-mediated mitochondrial damage is challenging, especially given the limited biological material available from nematodes.
Although in array analysis we did not detect caspase-8 activation, we found an increase of expression of Bid protein, a Bcl-2 family member, which has been shown to be a specific substrate of caspase-8 and to play a role in caspase-8-mediated mitochondrial damage and cell death [41].
These results demonstrated that ROS/GSK-3 β-mediated mitochondrial damage participated in glutamate-induced cytotoxicity.
The requirement of Bcl-2 for mutSOD1-mediated mitochondrial damage was confirmed in cells in situ.
Bax translocation from the cytosol to the mitochondria may be involved in triptolide-mediated mitochondrial damage and apoptosis.
ABT-737 may not fully restore NK-induced apoptosis in these cells but Bax/Bak-mediated mitochondrial damage could still induce caspase-independent death.
As ATP depletion is the direct consequence of oxidative damage to mitochondrial membranes and is a hallmark of necrotic cell death, our results strongly suggest that H2O2-mediated mitochondrial damage and necrotic cell death are iron dependent.
It is believed that one mechanism by which Bcl-2 may function as an anti-oxidant is through upregulation of GSH, leading to rapid detoxification of reactive oxygen species and inhibition of free radical-mediated mitochondrial damage.
