Severe reductions in transcripts for cytochrome c oxidase during erythropoiesis in vitro do not lead to inactive mitochondria in reticulocytes.

At some stage during erythroid cell differentiation proliferation of the cell stops and its organelles are removed and degraded. We wanted to know how mitochondrial function correlated with the synthesis of products necessary for functional mitochondria. We studied the time course of the presence of a nuclear and a mitochondrial transcript for the mitochondrial enzyme cytochrome c oxidase as well as that of the enzyme activity itself in differentiating murine splenic erythroid progenitors (erythroid colony-forming units, CFU-E) in vitro. Whereas the amount of total RNA as well as the transcripts for subunits II and IV of cytochrome c oxidase (COX II and COX IV) per cell decreased to low levels, the amount of globin mRNA increased from zero in CFU-E (t = 0) to high levels in late erythroblasts (21 h). Thus, RNA synthesis as such was not inhibited. The cytochrome c oxidase activity also declined. In the total culture, total RNA as well as the mRNAs for COX II and IV decreased after 7 h. The enzyme activity increased until 21 h and decreased after that. The early decrease of the transcripts, followed after a lag phase of 14 h by a decrease in enzyme activity, ultimately does not result in inactive mitochondria in the reticulocyte stage, as was shown with a mitochondria-specific fluorescent probe.