Effects of Cortisone on Rat Liver Mitochondria* by Charles Upton

Biochemical studies indicate that a substantial decrease in mitochondrial ribonucleic acid (RNA) of rat liver cells occurs following parenteral administration of large doses of cortisone acetate (1). Reports have appeared indicating that carcinogens can also affect mitochondrial RNA content as well as their number (2, 3), while virus invasion of a cell alters mitochondrial morphology (4). Mitochondria appear to be the locus of action of both the Krebs tricarboxylic acid enzyme system and the cytochrome system. Alterations, therefore, in their numbers might have important implications with respect to cell physiology as influenced by cortisone. From 10 to 20 per cent of the total RNA of the cell (5) is regularly associated with hepatic mitochondria. Basophilic stains such as pyronine (6), toluidine blue (7), and gallocyanin chrome alum (8) appear to have an affinity for RNA, and in the normal liver cells they can be used to demonstrate considerable amounts of this material. When, however, they are used to stain liver cells from animals subjected to chemical injury (7), starvation (9), or cortisone treatment (1, 10--13) one observes a marked depletion in basophilic material. To determine whether the fall in mitochondrial RNA following cortisone administration represents a decrease in mitochondrial numbers or merely a loss of RNA, the studies described below were undertaken. A comparison of mitochondrial numbers was made between normal rat liver and liver from rats that had received cortisone. Three experimental approaches were used: 1. Small blocks of rat liver were fixed in an osmic acid-containing mixture, stained appropriately, and examined for mitochondria. 2. Fresh, unstained, whole liver cells were examined for mitochondria with the phase microscope. 3. Mitochondrial and nuclear counts were performed on fresh whole liver homogenates.