Search

1. Effects of short-term and long-term administration of cycloheximide on rat liver mitochondrial protein synthesis have been examined and were found to be different. 2. Long-term administration of cycloheximide resulted in inhibition of total cellular protein synthesis including that of mitochondria while, at short-term intervals, 8–10% of mitochondrial protein synthesis was cycloheximide-resistant. 3. The inhibitory effect was also reflected in terms of protein synthesizing ability of mitochondria in vitro, the inhibition becoming apparent at 40 min and showing progressive increase with time. 4. The observed inhibition of mitochondrial protein synthesis by cycloheximide was not due to either inhibition of energy metabolism or alteration of amino-acid pool. 5. Cycloheximide did not enter mitochondria or sonic preparation under conditions in vitro. On the other hand, after administration of [³H]cycloheximide, significant quantities of the label were found to be associated with mitochondria and mitoribosomes. 6. These results indicated that cycloheximide reached the site of action in mitochondria under conditions in vivo but was unable to do so in vitro. 1. The results are discussed to elucidate the possible mechanisms involved in the inhibition of truly mitochondrial protein synthesis by cycloheximide. [ABSTRACT FROM AUTHOR]

Thyroid-status-dependent changes in lipid/phospholipid profiles in rat liver mitochondria were examined and attempts were made to correlate the observed changes with kinetic parameters of succinate-2,6-dichloroindophenol reductase (SDR) and membrane fluidity. Thyroidectomy caused substantial decrease in the total phospholipid and cholesterol contents; the proportion of all phospholipid components was also decreased significantly (50–100% decrease). The energy of activation, E1, for SDR decreased with a concomitant increase in the membrane fluidity. Treatment with physiologic doses or replacement doses of L-thyroxine resulted in partial restoration of lipid/phospholipid components. However, the SDR activity decreased with a simultaneous elevation in the phase-transition temperature and significant decreases in E1 and E2. Treatment with L-thyroxine restored membrane fluidity to almost euthyroid values. Regression analysis suggested a role for phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol microdomains in modulating the SDR activity. Membrane fluidity was strongly correlated with total phospholipid, cholesterol, diphosphatidylglycerol and phosphatidyl-inositol, and the ratio of cholesterol/total phospholipid (mol/mol). [ABSTRACT FROM AUTHOR]