Determinants of mitochondrial O2 dependence in kidney.
The O2 dependence of mitochondrial cytochromes was studied in suspensions of isolated rat kidney cells to examine the determinants of renal mitochondrial function. Direct spectroscopy of the oxidation of cytochromes c + c1, a + a3, and b561 + b566 showed that oxidation-reduction changes of the entire electron transport chain occur over the same range of O2 concentrations; this suggests that the mitochondrial cytochromes function as a single unit in response to O2 changes. Half-maximal oxidation (P50 value) of cytochrome c + c1 in intact cells was 3.6 microM but was only 0.45 microM in isolated renal cortex mitochondria under state 3 conditions. This is consistent with the existence of a substantial O2 concentration gradient from the extracellular space to the region around the mitochondria under hypoxic conditions. Comparison with results for digitonin-treated cells under state 3 conditions indicates that the distribution of mitochondria within the cellular structure is an important determinant of the cellular O2 dependence. In addition, the mitochondrial O2 dependence varies as a function of cellular respiration rate. Stimulation of the O2 consumption with either a protonophore, carbonyl cyanide p-trifluoromethoxyphenylhydrazone, or a sodium ionophore, nystatin, increased the P50 value. Conversely, inhibition of ATP consumption by Na+-K+-ATPase with ouabain, or inhibition of mitochondrial electron transport with antimycin A, decreased the P50 value. Thus the O2 concentration required for mitochondrial function in the kidney is affected by mitochondrial distribution within the cell as well as by the functional demands imposed on the cell.
Aw
T Y
TY
Wilson
E
E
Hagen
T M
TM
Jones
D P
DP
D000818:Animals; D002451:Cell Compartmentation; D003580:Cytochromes / Q000378:metabolism; D007668:Kidney / Q000378:metabolism* / Q000648:ultrastructure; D008928:Mitochondria / Q000378:metabolism*; D009761:Nystatin / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D003580:Cytochromes; D009761:Nystatin; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D010100:Oxygen