THE ORIGIN AND COMPOSITION OF PEROXIDASE-POSITIVE GRANULES IN CYSTEAMINE-TREATED ASTROCYTES IN CULTURE

Gomori astrocytes, which are prominent in periventricular regions of the brain, contain inclusions that stain with Gomori dyes, and exhibit an orange-red autofluorescence and a non-enzymatic peroxidase activity. Recently, such astrocytes have been induced in dispersed glial cultures by exposure to cysteamine. Using these cells, we have shown that the peroxidase-positive inclusions (Gomori bodies) are multicompartmental, that iron co-localizes with the peroxidase activity, and that the iron is often segregated in one of the compartments of the body. The goal of the present study was to determine the origin and process of formation of these bodies. The results indicate that cysteamine induces aberrations in mitochondrial structure associated with the acquisition of iron and the associated peroxidase activity. Mitochondria thus transformed appear to initiate an autophagic process in which they, and adjacent structures, are sequestered. The presence of acid phosphatase activity in a number of mature Gomori bodies attests to the participation of lysosomal elements in this process. These results indicate, therefore, that the Gomori body is a complex autophagosome in which the iron-containing compartments, putatively responsible for the peroxidase activity, represent undegraded transformed mitochondria.