Accumulation of calcium in the mitochondria of rat liver parenchymal cells at 16 and 24 hours after poisoning with carbon tetrachloride is associated with an increase in amount of liver inorganic phosphate, the persistence of mitochondrial adenosine triphosphatase activity, and the formation of electron-opaque intramitochondrial masses in cells with increased calcium contents. These masses, which form within the mitochondrial matrix adjacent to internal mitochondrial membranes, resemble those observed in isolated mitochondria which accumulate calcium and inorganic phosphate; are present in a locus similar to that of electron opacities which result from electron-histochemical determination of mitochondrial ATPase activity; and differ in both appearance and position from matrix granules of normal mitochondria. After poisoning, normal matrix granules disappear from mitochondria prior to their accumulation of calcium. As calcium-associated electron-opaque intramitochondrial masses increase in size, mitochondria degenerate in appearance. At the same time, cytoplasmic membrane systems of mid-zonal and centrilobular cells are disrupted by degranulation of the rough endoplasmic reticulum and the formation of labyrinthine tubular aggregates. The increase in amount of inorganic phosphate in rat liver following poisoning is balanced by a decreased amount of phosphoprotein. These chemical events do not appear to be related, however, as the inorganic phosphate accumulated is derived from serum inorganic phosphate.

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