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, a nd acute mitochondrial toxicity of iron in normal rats on the other su ggest a complex relationship between mitochondrial function and iron. Renal cortical mitochondrial respiratory function was therefore invest igated in RK and iron-loaded rats. State 4 (resting) respiration was i ncreased in RK rats (49 fl us 43 +/- 1 natom 0/min, P<0.001) in compar ison to control. Mitochondrial enzyme activity was lower in RK than co ntrol rats (e.g. succinate dehydrogenase 158.2 +/- 13.6 vs 237.2 +/- 1 7.4 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 mito chondrial enzyme activity (e.g. cytochrome oxidase 362.0 +/- 32.8 vs 1 85.0 +/- 46.6 Delta log[cyt C]/min/mg/prot, P<0.05) in control rats, b ut RK rats were more resistant to injury and there was no change in mi tochondrial enzyme activity. Mitochondrial fragility was similar in RK and control rats, and in both was unaffected by iron-loading. In conc lusion, rates of resting mitochondrial respiration are increased in pa rtially 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.