Recruitment of mitochondria into apoptotic signaling correlates with the presence of inclusions formed by amyotrophic lateral sclerosis-associated SOD1 mutations
Kai Y Soo, Julie D Atkin, Malcolm K Horne, Phillip Nagley
JOURNAL OF NEUROCHEMISTRY | WILEY | Published : 2009
Mutations in Cu, Zn-superoxide dismutase 1 (SOD1) are associated with degeneration of motor neurons in the disease, familial amyotrophic lateral sclerosis. Intracellular protein inclusions containing mutant SOD1 (mSOD1) are associated with disease but it is unclear whether they are neuroprotective or cytotoxic. We report here that the formation of mSOD1 inclusions in a motor neuron-like cell line (NSC-34) strongly correlates with apoptosis via the mitochondrial death pathway. Applying confocal microscopic analyses, we observed changes in nuclear morphology and activation of caspase 3 specifically in cells expressing mSOD1 A4V or G85R inclusions. Furthermore, markers of mitochondrial apoptosi..View full abstract
This work was supported by the National Health and Medical Research Council of Australia, the Bethlehem Griffiths Research Foundation, a Henry H. Roth Charitable Foundation grant for MND Research, and a Fellowship (to JDA) from the Motor Neuron Disease Research Institute of Australia.