Abstract
Mitochondria contribute to neuronal function not only via their ability to generate ATP, but also via their ability to buffer large Ca2+ loads. This review summarizes evidence that mitochondrial Ca2+ sequestration is especially important for sustaining the function of vertebrate motor nerve terminals during repetitive stimulation. Motor terminal mitochondria can sequester large amounts of Ca2+ because they have mechanisms for limiting both the mitochondrial depolarization and the increase in matrix free [Ca2+] associated with Ca2+ influx. In mice expressing mutations of human superoxide dismutase −1 (SOD1) that cause some cases of familial amyotrophic lateral sclerosis (fALS), motor terminals degenerate well before the death of motor neuron cell bodies. This review presents evidence for early and progressive mitochondrial dysfunction in motor terminals of mutant SOD1 mice (G93A, G85R). This dysfunction would impair mitochondrial ability to sequester stimulation-associated Ca2+ loads, and thus likely contributes to the early degeneration of motor terminals.
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Barrett, E.F., Barrett, J.N. & David, G. Mitochondria in motor nerve terminals: function in health and in mutant superoxide dismutase 1 mouse models of familial ALS. J Bioenerg Biomembr 43, 581–586 (2011). https://doi.org/10.1007/s10863-011-9392-1
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DOI: https://doi.org/10.1007/s10863-011-9392-1