Mitochondrial function in partially nephrectomized rats

Previous demonstrations of increased oxygen consumption and renal iron accumulation in partially nephrectomized (RK) rats on the one hand, and acute mitochondrial toxicity of iron in normal rats on the other suggest a complex relationship between mitochondrial function and iron. Renal cortical mitochondrial respiratory function was therefore investigated in RK and iron-loaded rats. State 4 (resting) respiration was increased in RK rats (49 fl us 43 +/- 1 natom 0/min, P<0.001) in comparison to control. Mitochondrial enzyme activity was lower in RK than control rats (e.g. succinate dehydrogenase 158.2 +/- 13.6 vs 237.2 +/- 17.4 Delta log[cyt C]/min/mg/prot, P<0.01). Acute iron-loading impaired creatinine clearance (1.39 +/- 0.01 vs 0.40 +/- 0.29 mL/min) and mitochondrial enzyme activity (e.g. cytochrome oxidase 362.0 +/- 32.8 vs 185.0 +/- 46.6 Delta log[cyt C]/min/mg/prot, P<0.05) in control rats, but RK rats were more resistant to injury and there was no change in mitochondrial enzyme activity. Mitochondrial fragility was similar in RK and control rats, and in both was unaffected by iron-loading. In conclusion, rates of resting mitochondrial respiration are increased in partially nephrectomized rats, despite reduced intrinsic activity of two iron-dependent mitochondrial enzymes. Mitochondrial function is more resistant to acute injury with iron in partially nephrectomized rats.