Cerebrosides and psychosine disrupt mitochondrial functions.

Glucocerebroside and galactocerebroside increased the respiratory rate of liver and brain mitochondria by 33-400% and produced an average 30% decrease in oxidative phosphorylation. Psychosine stimulated mitochondrial respiration 66-700%. At concentrations over 100 micrograms/mg mitochondrial protein, oxidative phosphorylation was completely inhibited. Atractyloside did not prevent the respiratory stimulation. Ca2+ transport was blocked and addition of ATP could not overcome this inhibition. The possible deleterious effect of glycosphingolipids on the conformation of the mitochondrial membrane and cellular bioenergetics is discussed in relation to the toxicity of accumulating glycosphingolipids in Gaucher and Krabbe diseases.