Effect of oxalate on function of kidney mitochondria.
The effects of oxalate on kidney mitochondria were evaluated in vitro to test whether oxalate exposure leads to derangement(s) in mitochondrial function that could in turn promote the formation of kidney stones. Our previous studies demonstrated that oxalate is transported across the mitochondrial membrane via the dicarboxylate carrier. The present studies indicated that oxalate competitively inhibits the uptake and oxidation of exogenous malate and succinate in isolated mitochondria but has no effect on mitochondrial respiration in the presence of a mixture of glutamate plus malate or glutamate plus pyruvate. Oxalate attenuates the increase in mitochondrial respiration produced by the uncoupler CCCP or by the Ca2+ ionophore A23187, and the latter effect is more pronounced in kidney than in liver mitochondria. The apparent Ki of oxalate for the response to Ca2+ ionophore is 1.9 +/- 0.3 mM in kidney and 6.1 +/- 0.2 mM in liver mitochondria. Similarly, the ability of oxalate to attenuate calcium-induced swelling of mitochondria is more dramatic in kidney than in liver mitochondria (apparent KiS of 1.7 +/- 0.1 and 18.2 +/- 0.7 mM, respectively). Oxalate has no effect on the rate of calcium uptake by energized mitochondria or on the rate of ruthenium red-insensitive calcium efflux from mitochondria in either tissue. The above findings indicate that oxalate interacts with the inner mitochondrial membrane or with processes controlling membrane integrity to a greater extent in kidney than liver mitochondria. The effects of oxalate on membrane permeability or integrity may be more important than its effects on mitochondrial energy production or calcium sequestration in the pathogenesis of calcium oxalate microlith formation in the kidney.
Strzelecki
T
T
University of Massachusetts Medical School, Worcester 01655.
McGraw
B R
BR
Scheid
C R
CR
Menon
M
M
D000818:Animals; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000187:drug effects; D007668:Kidney / Q000378:metabolism*; D007669:Kidney Calculi / Q000209:etiology; D008928:Mitochondria / Q000187:drug effects; D008930:Mitochondria, Liver / Q000187:drug effects; D010070:Oxalates / Q000494:pharmacology*; D019815:Oxalic Acid; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D010070:Oxalates; D019815:Oxalic Acid