Up-regulation of the plasma membrane oxidoreductase as a prerequisite for the viability of human Namalwa rho 0 cells.

We have studied aspects of the regulatory interrelationship between the plasma membrane oxidoreductase (PMOR) system and the mitochondrial respiratory capacity of human Namalwa cells. Although the role of mitochondria in the maintenance of cellular redox and energetic states is well established, the PMOR system in comparison is a poorly characterized enzyme system whose functions, particularly in relation to cellular metabolism, have not been clearly elucidated. Therefore we compared the PMOR and mitochondrial respiratory activities of human Namalwa cells during the induction by ethidium bromide treatment of rho 0 cells, which lack a functional mitochondrial respiratory system. The plasma membrane NADH-ferricyanide reductase activity of the PMOR system was found to increase in a stepwise manner concomitant with a decline in cellular mitochondrial respiratory activity. Addition of p-chloromercuriphenylsulfonic acid to the culture medium, at a concentration totally inhibiting the plasma membrane NADH-ferricyanide reductase in vitro, leads to cell death of rho 0 but not of rho + cells. Thus, the up-regulation of a functional PMOR system is a necessary phenomenon in maintaining the viability of mammalian rho 0 cells.