12/15-Lipoxygenase targets neuronal mitochondria under oxidative stress
Article first published online: 8 SEP 2009
© 2009 The Authors. Journal Compilation © 2009 International Society for Neurochemistry
Journal of Neurochemistry
Volume 111, Issue 3, pages 882–889, November 2009
How to Cite
Pallast, S., Arai, K., Wang, X., Lo, E. H. and Van Leyen, K. (2009), 12/15-Lipoxygenase targets neuronal mitochondria under oxidative stress. Journal of Neurochemistry, 111: 882–889. doi: 10.1111/j.1471-4159.2009.06379.x
- Issue published online: 12 OCT 2009
- Article first published online: 8 SEP 2009
- Received June 25, 2009; revised manuscript received August 7, 2009; accepted August 30, 2009.
- cytochrome c;
- reactive oxygen species
12/15-Lipoxygenase (12/15-LOX) is an important mediator of brain injury following experimental stroke in rodents. It contributes to neuronal death, but the underlying mechanism remains unclear. We demonstrate here that in neuronal HT22 cells subjected to glutamate-induced oxidative stress, 12/15-LOX damages mitochondria, and this represents the committed step that condemns the cell to die. Importantly these events, including breakdown of the mitochondrial membrane potential, the production of reactive oxygen species, and cytochrome c release, can all be replicated by incubation of 12/15-LOX with mitochondria in vitro, without the need to add other cytosolic factors. Proteasome activity is required downstream of mitochondrial damage to complete the cell death cascade, but proteasome inhibition is only partially protective. These findings position 12/15-LOX as the central executioner in an oxidative stress-related neuronal death program.