ABSTRACT
Mitochondrial involvement in amyotrophic lateral sclerosis (ALS) was initially suggested by circumstantial evidence from ultrastructural studies in human autopsies. Afifi et al. (1) first reported abnormal mitochondrial morphology in atrophic muscles of ALS patients in 1966. They observed aggregates of mitochondria in subsarcolemmal regions of muscle fibers. The mitochondria were dense and large, and distributed in a pattern of ‘‘sentinel mitochondria’’ along the Z line, perpendicular to the myofibrils. Other studies have supplied a continuous stream of evidence suggesting the involvement of mitochondrial abnormality in the pathogenesis of ALS. Mitochondrial abnormalities and dysfunction have been reported in liver biopsies and peripheral blood lymphocytes from individuals with sporadic ALS (2-4). Atsumi (5) found a reduction in the number of mitochondria in intramuscular nerves. Siklos et al. (6) found increased mitochondrial volume and elevated calcium levels within the mitochondria from muscle biopsy of ALS patients. Although early studies in the central nervous system (CNS) focused on neurofilament accumulation in proximal axons because of their conspicuous presence, careful examination of the published EM micrographs reveals numerous vacuolated mitochondria among swirls of disorganized neurofilaments in both sporadic and familial cases (7). Other studies found numerous abnormal mitochondria in upper and lower motor neurons in human ALS cases (8-10).
