Cellular mechanisms involved in multiple neurodegenerative diseases converge on 
mitochondria to induce overproduction of reactive oxygen species, damage to 
mitochondria, and subsequent cytochrome c release. Little is currently known 
regarding the contribution mitochondrial dynamics play in cytochrome c release 
following oxidative stress in neurodegenerative disease. Here we induced 
oxidative stress in the HT22 cell line with glutamate and investigated key 
mediators of mitochondrial dynamics to determine the role this process may play 
in oxidative stress induced neuronal death. We report that glutamate treatment 
in HT22 cells induces increase in reactive oxygen species (ROS), release of the 
mitochondrial fusion protein Opa1 into the cytosol, with concomitant release of 
cytochrome c. Furthermore, following the glutamate treatment alterations in cell 
signaling coincide with mitochondrial fragmentation which culminates in 
significant cell death in HT22 cells. Finally, we report that treatment with the 
antioxidant tocopherol attenuates glutamate induced-ROS increase, release of 
mitochondrial Opa1 and cytochrome c, and prevents cell death.