Jan 21, 2011

Metabolic and functional differences between brain and spinal cord mitochondria underlie different predisposition to pathology

American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Alexander PanovH L Bonkovsky

Abstract

Mitochondrial dysfunctions contribute to neurodegeneration, the locations of which vary among neurodegenerative diseases. To begin to understand what mechanisms may underlie higher vulnerability of the spinal cord motor neurons in amyotrophic lateral sclerosis, compared with brain mitochondria, we studied three major functions of rat brain mitochondria (BM) and spinal cord mitochondria (SCM) mitochondria: oxidative phosphorylation, Ca(2+) sequestration, and production of reactive oxygen species (ROS), using a new metabolic paradigm (Panov et al., J. Biol. Chem. 284: 14448-14456, 2009). We present data that SCM share some unique metabolic properties of the BM. However, SCM also have several distinctions from the BM: 1) With the exception of succinate, SCM show significantly lower rates of respiration with all substrates studied; 2) immunoblotting analysis showed that this may be due to 30-40% lower contents of respiratory enzymes and porin; 3) compared with BM, SCM sequestered 40-50% less Ca(2+), and the total tissue calcium content was 8 times higher in the spinal cord; 4) normalization for mitochondria from 1 g of tissue showed that BM can sequester several times more Ca(2+) than was available in the brain tissue, whereas SCM ...Continue Reading

  • References43
  • Citations14

Citations

Mentioned in this Paper

Metabolic Process, Cellular
Calcium [EPC]
Apoptosis, Intrinsic Pathway
Enzymes, antithrombotic
Calcium
Malignant Neoplasm of Spinal Cord
Neurons
Brain
Electron Transport
Succinates

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