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Mutations in the cytochrome  c  gene ( CYCS ) cause autosomal dominant thrombocytopenia by an unknown mechanism. While attempting to generate megakaryoblastic cell lines exogenously expressing cytochrome  c  variants, we discovered that endogenous cytochrome  c  expression increased both upon induction of differentiation with the phorbol ester phorbol 12-myristate 13-acetate (PMA), and as cell density increased. A concomitant increase in cytochrome  c  oxidase subunit II in response to PMA, but not cell higher cell density, suggests upregulation of the mitochondrial respiratory chain may be a specific feature of differentiation. These results highlight the likely importance of cytochrome  c  in both differentiating and proliferating cells, and illustrate the unsuitability of megakaryoblastic lines for modeling  CYCS -associated thrombocytopenia.

plos one

Differentiation and cell density upregulate cytochrome c levels in megakaryoblastic cell lines: Implications for analysis of CYCS-associated thrombocytopenia