Effects of Phthalate Esters on the Latent ATPase and Swelling of Mitochondria

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Abstract
Phthalate esters have shown to stimulate the latent ATPase [EC 3.6.1.3] activity and induce mitochondrial swelling. Among the tested phthalate esters, di-n-butyl phthalate (DBP) exhibited the greatest activity, and the activity decreased progressively as the alkyl chain was lengthened or shortened. The DBP-stimulated ATPase was oligomycin-sensitive. The degree of stimulation of the ATPase was proportional to the extent of mitochondrial swelling induced by DBP in 0.1 M Tris-HCl (pH 7.2) containing 0.25 M sucrose. However, the swelling was dependent on the tonicity of the solution or the concentration of chloride ions, while the stimulation of ATPase was independent of these factors. Swelling was strongly induced by DBP at slightly acidic rather than neutral or alkaline pH. The pH-activity curve of DBP-stimulated ATPase was in inverse correlation with that of swelling, which showed a rather flat maximum at pH 8.0. When bovine serum albumin (BSA) was added to a solution containing mitochondria before addition of DBP, swelling was no longer caused by DBP, though the latent ATPase was stimulated to the same extent in the absence of added BSA.