ABSTRACT
This chapter reviews the current evidence supporting the involvement of mitochondria in amyotrophic lateral sclerosis (ALS) and discusses the potential implications in the pathogenesis of this neurodegenerative disease. Morphologic and ultrastructural abnormalities of mitochondria have been observed in autopsies of patients with sporadic disorder (SALS). In eukaryotic cells, superoxide is a normal byproduct of aerobic respiration and it is produced by oxidative phosphorylation in the mitochondria. A development in the field that has helped in shedding some light on the mechanisms of mitochondrial dysfunction caused by mutant SOD1 is the finding that a proportion of SOD1 is localized in the mitochondria. A number of toxic effects of mutated SOD1 have been proposed, including impairment of mitochondrial energy metabolism and apoptosis. Mitochondria are the site of initiation of the intrinsic apoptotic pathway, which is activated by the release of pro-apoptotic factors from mitochondria and can be either caspase-dependent or caspase-independent.
