MITOCHONDRIAL OXIDATIVE-PHOSPHORYLATION AND INTRACELLULAR GLUTATHIONECOMPARTMENTATION DURING RAT-LIVER REGENERATION

The rate of mitochondrial oxidative phosphorylation and the cytosolic and mitochondrial total and oxidized glutathione concentrations were s tudied in regenerating rat livers after partial (70%) hepatectomy. The rate of mitochondrial oxidative phosphorylation progressively decreas ed during the early prereplicative phase of liver regeneration. This w as accompanied by a progressive decrease in mitochondrial, but not cyt osolic, glutathione concentration. Twenty-four hours after partial hep atectomy, both the rate of adenosine triphosphate (ATP) synthesis and the amount of mitochondrial glutathione were depressed by 50% with res pect to controls (sham-operated animals). During the second replicativ e phase, both the oxidative phosphorylation rate and mitochondrial glu tathione concentration-were recovered; however, the kinetics of the re covery were different, being the total amount of mitochondrial glutath ione completely restored 48 hours after partial hepatectomy, whereas 7 2 hours were needed for the recovery of oxidative phosphorylation. The decrease in the rate of oxidative phosphorylation, during the early p hase of liver regeneration, appeared to be secondary to the decreased content of the catalytic subunit beta-F-1 of the ATP synthase complex, which in turn was shown to be linearly related to the decrease of int ramitochondrial glutathione. These observations suggest that the two p henomena may be due to the previously reported increased free radical production during the early phase of liver regeneration. The depressio n of mitochondrial glutathione after partial hepatectomy may play a co ntributory role in structural and functional alterations of mitochondr ia occurring in the first retrodifferential phase of liver regeneratio n.