Abstract
Abundant evidence indicates that mitochondrial dysfunction and Ca(2+) dysregulation contribute to the muscle denervation and motor neuron death that occur in mouse models of familial amyotrophic lateral sclerosis (fALS). This perspective considers measurements of mitochondrial function and Ca(2+) handling made in both motor neuron somata and motor nerve terminals of SOD1-G93A mice at different disease stages. These complementary studies are integrated into a model of how mitochondrial dysfunction disrupts handling of stimulation-induced Ca(2+) loads in presymptomatic and end-stages of this disease. Also considered are possible mechanisms underlying the findings that some treatments that preserve motor neuron somata fail to postpone degeneration of motor axons and terminals.