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12/15‐Lipoxygenase targets neuronal mitochondria under oxidative stress
Author(s) -
Pallast Stefanie,
Arai Ken,
Wang Xiaoying,
Lo Eng H.,
Van Leyen Klaus
Publication year - 2009
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.06379.x
Subject(s) - mitochondrion , oxidative stress , microbiology and biotechnology , programmed cell death , reactive oxygen species , cytosol , apoptosis , oxidative phosphorylation , glutamate receptor , biology , cytochrome c , proteasome , mediator , chemistry , biochemistry , enzyme , receptor
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.