Respiratory characteristics of neonatal rat hepatocytes

Mitochondrial function was studied in isolated hepatocytes from newborn rats to determine the substrate requirements and oxygen dependence of perinatal respiratory activity. The results show that neonatal O2 consumption is markedly dependent on succinate availability; the respiration rate was extremely low in the absence of exogenous substrates, but was stimulated 15-fold by succinate, with half-maximal stimulation of O2 consumption at 0.5 mM succinate. Significant inhibition of respiration by low concentrations of antimycin A suggests that the succinate-induced increase in cellular O2 consumption was primarily due to mitochondrial activity. In contrast, other potential metabolic fuels at comparable concentrations (2.5 to 10 mM) gave less than 2-fold stimulation. Half-maximal oxidation (P50 value) of the mitochondrial cytochromes occurred at very low O2 concentrations and was sensitive to factors that alter cellular O2 consumption. The P50 for cytochrome c oxidation (0.52 microM with 1.5 mM succinate) was, respectively, increased or decreased by additions of succinate or antimycin A. These distinctly lower P50 values for mitochondrial function in neonatal cells compared to adult cells could be a major factor in the ability of fetal and neonatal cells to tolerate relatively low O2 concentrations.