Mitochondrial bioenergetics during the initiation of mercuric chloride-induced renal injury. I. Direct effects of in vitro mercuric chloride on renal mitochondrial function.
Increasing data suggest that mitochondrial dysfunction may be an important early component of nephrotoxin-induced changes in renal cell function and viability. This study was designed to obtain more detailed information about the effects on several basic bioenergetic parameters of the direct interaction of Hg2+ with renal cortical mitochondria in vitro as a necessary prelude to studies of mitochondrial functional changes after treatment with mercuric chloride in vivo. Beginning at a threshold level of 2 nmol of Hg2+/mg of mitochondrial protein, Hg2+ induced marked stimulation of State 4 respiration, mild inhibition of State 3 respiration, and 2,4-dinitrophenol uncoupled respiration, a striking increase in atractyloside-insensitive ADP uptake and stimulation of both basal- and Mg2+-activated oligomycin-sensitive mitochondrial ATPase activity. These effects of Hg2+ could be prevented and reversed by the sulfhydryl reagent dithioerythritol and by albumin but were not affected by Mg2+. Detailed studies on the addition of HgCl2 to the preparation at different stages of the mitochondrial isolation procedure demonstrated that the presence of other proteins decreased mitochondrial Hg2+ binding, that the Hg2+ was not readily washed off the mitochondria by nonprotein-containing solutions, and that prolonged exposure of mitochondria to Hg2+ during the isolation procedure did not markedly alter its functional effects or their reversibility as assessed on the final mitochondrial preparation. These data provide an important basis for critically assessing the changes in function of mitochondria isolated after in vivo treatment with mercuric chloride.
D000244:Adenosine Diphosphate / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008627:Mercuric Chloride; D008628:Mercury / Q000378:metabolism / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D008627:Mercuric Chloride; D000244:Adenosine Diphosphate; D000251:Adenosine Triphosphatases; D008628:Mercury; D008274:Magnesium