Structural changes in mitochondria induced by uncoupling reagents. The response to proteolytic enzymes.
Interaction of uncoupling reagents with bovine serum albumin markedly inhibited its hydrolysis by proteolytic enzymes. The inhibition presumably is due to conformational transitions in the protein substrate induced by the binding of the ligand-uncoupling reagents. The proteolysis of casein, a protein that does not bind these reagents, was not affected, indicating that the proteinases themselves were not inactivated. In contrast, interaction of uncoupling reagents with freshly isolated rat liver mitochondria enhanced their susceptibility to proteolytic enzymes. This was shown by an increase in the release of ninhydrin-reacting material, by an increase in free acid groups and by a decrease in the turbidity of the mitochondrial suspensions. These effects, although opposite in direction to those obtained with albumin, are also presumed to indicate structural changes in the mitochondrial proteins and a disorganization of the protein-phospholipid complex. It is suggested that such structural alterations are expressed functionally as the uncoupling of oxidative phosphorylation.
D000654:Amobarbital / Q000494:pharmacology; D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D002122:Calcium Chloride / Q000494:pharmacology; D002364:Caseins; D055598:Chemical Phenomena; D002621:Chemistry; D001728:Dicumarol / Q000494:pharmacology; D004140:Dinitrophenols / Q000494:pharmacology; D006834:Hydrazines / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008930:Mitochondria, Liver / Q000187:drug effects*; D009840:Oligomycins / Q000494:pharmacology; D010085:Oxidative Phosphorylation; D010447:Peptide Hydrolases / Q000378:metabolism*; D010636:Phenols / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D012402:Rotenone / Q000494:pharmacology; D012710:Serum Albumin, Bovine; D013053:Spectrophotometry; D013997:Time Factors; D014357:Trypsin / Q000378:metabolism; D014449:Tyrothricin / Q000494:pharmacology
D001562:Benzimidazoles; D002364:Caseins; D004140:Dinitrophenols; D006834:Hydrazines; D009840:Oligomycins; D010636:Phenols; D012402:Rotenone; D014449:Tyrothricin; D012710:Serum Albumin, Bovine; D000968:Antimycin A; D001728:Dicumarol; D010447:Peptide Hydrolases; D014357:Trypsin; D000654:Amobarbital; D002122:Calcium Chloride