UP-REGULATION OF THE PLASMA-MEMBRANE OXIDOREDUCTASE AS A PREREQUISITEFOR THE VIABILITY OF HUMAN NAMALWA RHO(0) CELLS

We have studied aspects of the regulatory interrelationship between th e plasma membrane oxidoreductase (PMOR) system and the mitochondrial r espiratory capacity of human Namalwa cells. Although the role of mitoc hondria in the maintenance of cellular redox and energetic states is w ell established, the PMOR system in comparison is a poorly characteriz ed enzyme system whose functions, particularly in relation to cellular metabolism, have not been clearly elucidated. Therefore we compared t he PMOR and mitochondrial respiratory activities of human Namalwa cell s during the induction by ethidium bromide treatment of rho(0) cells, which lack a functional mitochondrial respiratory system. The plasma m embrane NADH-ferricyanide reductase activity of the PMOR system was fo und to increase in a stepwise manner concomitant with a decline in cel lular mitchondrial respiratory activity. Addition of p-chloromercuriph enylsulfonic acid to the culture medium, at a concentration totally in hibiting the plasma membrane NADH-ferricyanide reductase in vitro, lea ds to cell death of rho(0) but not of rho(+) cells. Thus, the up-regul ation of a functional PMOR system is a necessary phenomenon in maintai ning the viability of mammalian rho(0) cells.