Mitochondrial enzyme activity in amyotrophic lateral sclerosis: Implications for the role of mitochondria in neuronal cell death

• Published in: Annals of neurology 1999-11, Vol.46 (5), p.787-790
• Main Authors: Borthwick, Gillian M., Johnson, Margaret A., Ince, Paul G., Shaw, Pamela J., Turnbull, Douglass M.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Animals; Biological and medical sciences; Cell Death; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; DNA, Mitochondrial - genetics; Electron Transport Complex IV - genetics; Electron Transport Complex IV - metabolism; Female; Humans; Male; Medical sciences; Mice; Middle Aged; Mitochondria - enzymology; Mitochondria - pathology; Motor Neuron Disease - enzymology; Motor Neuron Disease - genetics; Motor Neuron Disease - pathology; Motor Neurons - enzymology; Motor Neurons - pathology; Neurology; Reference Values; Spinal Cord - enzymology; Spinal Cord - pathology; Succinate Dehydrogenase - metabolism
• ISSN: 0364-5134; 1531-8249
• DOI: 10.1002/1531-8249(199911)46:5<787::AID-ANA17>3.0.CO;2-8

The mechanism of selective loss of motor neurons in amyotrophic lateral sclerosis (ALS) has not been clarified. Mitochondrial pathology is present in central nervous system tissue from ALS cases and occurs as an early event in a mouse model of ALS. We demonstrate that, in sporadic ALS, there is a selective decrease in the activity of the mitochondrial DNA–encoded enzyme cytochrome c oxidase in human spinal cord motor neurons. We propose that this may not only be important in neuronal cell death but could well be caused by oxidative damage to mitochondrial DNA leading to the accumulation of mitochondrial DNA mutations.