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

Ann Neurol. 1999 Nov;46(5):787-90. doi: 10.1002/1531-8249(199911)46:5<787::aid-ana17>3.0.co;2-8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Cell Death
  • DNA, Mitochondrial / genetics
  • Electron Transport Complex IV / genetics
  • Electron Transport Complex IV / metabolism*
  • Female
  • Humans
  • Male
  • 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
  • Reference Values
  • Spinal Cord / enzymology*
  • Spinal Cord / pathology
  • Succinate Dehydrogenase / metabolism*

Substances

  • DNA, Mitochondrial
  • Succinate Dehydrogenase
  • Electron Transport Complex IV