Selective changes in mitochondria respiratory properties in oxidative or glycolytic muscle fibers isolated from G93AhumanSOD1 transgenic mice

Cases of familial amyotrophic lateral sclerosis (FALS) are associated with mutations in cytosolic copper, zinc superoxide dismutase (SOD1). Total SOD activity and functional mitochondrial properties were studied in muscles an d nervous tissues of control and transgenic mice mimicking the disease. It was found that total SOD activity was lower in nervous tissues than in musc les in both transgenic and control mice. In addition SOD activity increased during progression of disease in muscle but not in nervous tissue of trans genic mice. Maximal oxygen consumption and apparent Km for ADP were decreas ed in mitochondria from transgenic soleus (an oxidative muscle). However th ere was no difference between control and transgenic mice in respiratory pa rameters of mitochondria in the EDL muscle (a glycolytic muscle). These fin dings indicate that oxidative stress due to SOD1 mutations could alter ener gy metabolism in FALS mice. thereby affecting primarily oxidative muscle of the limbs, independently of motoneuron loss. (C) 2001 Elsevier Science B.V . All rights reserved.