EFFECT OF PSYCHOSINE ON MITOCHONDRIAL-FUNCTION

The effect of psychosine on the rate of respiration at different segme nts of the electron transport chain, respiratory control ratio and the efficiency of phosphorylation was studied. The transfer of electrons through site I, site II and site III was studied independently. The tr ansfer through site I and site III was inhibited by psychosine, wherea s the transfer through site II was not inhibited. Cardiolipin, which i s essential for the electron transfer through site I and III, was impl icated to be responsible for the inhibition of electron transfer by ps ychosine, Electron carriers of site II are not sensitive to cardiolipi n, so psychosine could not inhibit the electron transfer through this site. The ADP/O ratio and respiratory control ratio were inhibited by psychosine showing that it has an uncoupler like effect. Mitochondria isolated from rat liver, kidney and brain behaved essentially the same way in their response to psychosine. Cytochrome c oxidase was signifi cantly inhibited by psychosine and the degree of inhibition was almost same in mitochondria and sub mitochondrial particles. The preence of outer membrane in mitochondria did not make any difference with respec t to the action of psychosine on electron transport chain. Psychosine interacts at site I and site III and a change in the lipid environment of the membrane is responsible for the mitochondrial dysfunctions ind uced by psychosine. This repreents a possible mechanism for the destru ction of cells in Gaucher's and Krabbe's disease.