Mitochondria and the pathogenesis of ALS

Evidence implicating mitochondria as playing a crucial role in both necrotic and apoptotic cell death is rapidly accumulating. Mitochondria are essential in controlling specific apoptosis pathways (Green and Reed, 1998). Mitochondrial calcium uptake is required for glutamate excitotoxicity and there is a correlation between increases in mitochondrial calcium and increases in free radical generation, which are linked with cell death (Stout et al ., 1998). The mitochondrial permeability transition pore may be crucial in both necrotic and apoptotic cell death. Activation of the permeability transition pore increases the mitochondrial membrane permeability to solids with a molecular mass of up to 1.5 kDa (Bernardi, 1999). It is activated by increases in calcium, and free radicals and cyclosporin A inhibits its activation. Cyclosporin A blocks neuronal damage produced by hypoglycaemia and ischaemia in vivo (Friberg et al ., 1998).A potential role of mitochondria in amyotrophic lateral sclerosis (ALS) is gaining increasing support. In this issue of Brain , Vielhaber and colleagues report further evidence implicating mitochondrial dysfunction in ALS (Vielhaber et al ., 2000). The authors examined muscle biopsies of patients with ALS, compared with normal controls and …