Reye's syndrome: plasma-induced alterations in mitochondrial structure and function

Preincubation of rat liver mitochondria with plasma from Reye's syndrome (RS) patients induces a transient stimulation of the State 4 respiratory rate of the oxidation of NAD-linked substrates which is followed by inhibition. A loss of nearly 90% of the intramitochondrial NAD⁺ and NADP⁺ is also seen. The respiratory rate cannot be stimulated upon subsequent addition of ADP, but can be fully restored upon the addition of either NAD⁺ or succinate (plus rotenone). The degree of effectiveness depends on the incubation time and the ratio of RS-plasma/mitochondrial protein. The RS-plasma effects can be eliminated by an inhibitor of mitochondrial Ca²⁺ transport (ruthenium red) or by a Ca²⁺ chelator (ethylene glycol bis(β-aminoethyl ether)N,N′-tetraacetic acid). Control plasma at a concentration of 2 mg dry wt per milligram of mitochondrial protein, or 30 μm Ca²⁺ gives no effect, but can reproduce the RS-plasma effects completely when a minute amount of allantoin (10^?11 mol/mg mitochondrial protein) is also present. We conclude that allantoin and Ca²⁺ can increase the permeability of mitochondrial membrane, and may be the key components responsible for the mitochondrial injuries produced by RS-plasma.