Effect of Reye's syndrome serum on the ultrastructure of isolated liver mitochondria.
Reye's syndrome (RS) is characterized by alterations in the ultrastructure of liver mitochondria and a generalized impairment of mitochondrial enzyme activity. Serum from RS patients impairs ATP formation and oxidative phosphorylation of isolated liver mitochondria. We examined the effect of serum from four RS patients (including mild and severe illnesses) to determine whether RS serum induces quantifiable morphometric changes in isolated liver mitochondria. RS serum expands the mitochondrial matrix (matrix = 85 to 91% of cross-sectional area, compared with 65 +/- 12% with control serum, p less than .01) and in many cases the matrix is less dense, cristae are less apparent, and mitochondrial shape is irregular. After incubation with RS serum, mitochondria are also slightly larger (range = 0.563 to 0.492 micron 2) than mitochondria incubated with serum from normal controls (0.421 +/- 0.303 micron 2). These changes are similar to those observed in vivo in RS. The effect of RS serum is largely irreversible, resembling the effect of an uncoupler of oxidative phosphorylation, and corresponds to the free fatty acid concentration in the serum, especially the concentration of serum dicarboxylic acids. Addition of comparable amounts of long chain dicarboxylic acids induces an irreversible expansion and some distortion of mitochondria comparable to that after the addition of RS serum. There is no correlation between alteration in ultrastructure and the presence of salicylates in the serum samples. The results indicate that dicarboxylic acids may play a role in the changes in mitochondrial ultrastructure that characterize RS.
Tonsgard
J H
JH
Department of Pediatrics and Neurology, Pritzker School of Medicine, University of Chicago, Illinois.
D002648:Child; D002675:Child, Preschool; D016883:Diabetic Ketoacidosis / Q000097:blood; D003998:Dicarboxylic Acids / Q000378:metabolism; D004140:Dinitrophenols; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006801:Humans; D007223:Infant; D008930:Mitochondria, Liver / Q000378:metabolism / Q000648:ultrastructure*; D010085:Oxidative Phosphorylation; D012202:Reye Syndrome / Q000097:blood* / Q000378:metabolism / Q000473:pathology; D014475:Uncoupling Agents
D003998:Dicarboxylic Acids; D004140:Dinitrophenols; D005230:Fatty Acids, Nonesterified; D014475:Uncoupling Agents