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These results support the hypothesis that Gomori-positive inclusions are autophagosomes in which mitochondria are prominent.

Astrocytes in subcortical regions of the mammalian brain progressively accumulate iron-rich, autofluorecent cytoplasmic inclusions as a function of aging. Cysteamine (CSH) accelerates the appearance of this senescent glial phenotype in situ and in primary rat astroglial cultures. Porphyrins have been implicated as the source of orange-red autofluorescence in these glial inclusions. Yet, CSH has been shown to suppress porphyrin-heme biosynthesis in cultured astroglia. To determine whether porphyrin biosynthesis or sequestration participates in the biogenesis of these glial inclusions, the porphyrin precursor, ³H-δ-aminolevulinic acid (³H-ALA) was administered to CSH-exposed and control rat astroglial cultures followed by light and electron microscopic autoradiography. Control cultures exhibited faint orange-red autofluorescence, intense ³H-ALA labeling, numerous normal mitochondria and few cytoplasmic inclusions. In these cells, ³H-ALA labeling largely occurred over normal mitochondria. The CSH-treated astroglia exhibited diminished ³H-ALA labeling and contained numerous orange-red autofluorescent inclusions. The latter manifested internal compartments delimited by double membranes characteristic of damaged mitochondria. The complement of normal mitochondria in the CSH-exposed cells was markedly reduced. In the CSH-treated cells, ³H-ALA labeling predominated over the large multi-compartmental inclusions. CSH attenuates de novo porphyrin-heme biosynthesis in astroglia but may induce punctate orange-red autofluorescence in the cytoplasm of these cells by promoting large numbers of damaged, porphyrin-containing mitochondria to form tight aggregates within the nascent gliosomes.