Participation of mitochondrial proliferation in morphological differentiation of murine mastocytoma cells

Abstract

Proliferation of a cold-sensitive cell-cycle mutant isolated from an undifferentiated murine mastocytoma line is reversibly arrested at the nonpermissive temperature of 33 °C, and the arrested cells undergo morphological differentiation as expressed by the formation of metachromatic granules. Following transfer of these mutant cells from the permissive temperature of 39.5 to 33 °C, a transient increase in both cytochrome c oxidase and DNA polymerase γ was observed, the ratio of total mitochondrial volume to cell volume nearly doubled within 6 days, and numbers of mitochondrial cross-sections per cellular crosssection as determined in electron micrographs underwent a threefold increase. Addition of chloramphenicol (100 μg/ml) to the mutant cell cultures 6 days prior to transfer from 39.5 to 33 °C prevented the increase in the ratio of total mitochondrial to cell volume. Furthermore, chloramphenicol markedly inhibited the increase in granule number per cell that normally is observed after transfer of cultures to 33 °C or during treatment with 1 m M butyrate. suggesting that mitochondrial proliferation may be an obligatory step in the process of morphological differentiation of these mastocytoma cells.