Cytochrome c-mediated apoptosis in cells lacking mitochondrial DNA - Signaling pathway involving release and caspase 3 activation is conserved

Mitochondria serve as a pivotal component of the apoptotic cell death machi nery. However, cells that lack mitochondrial DNA (rho(0) cells) retain appa rently normal apoptotic signaling. In the present study, we examined mitoch ondrial mechanisms of apoptosis in rho(0) osteosarcoma cells treated with s taurosporine. Immunohistochemistry revealed that rho(0) cells maintained a normal cytochrome c distribution in mitochondria even though these cells we re deficient in respiration. Upon staurosporine treatment, cytochrome c was released concomitantly with activation of caspase 3 and loss of mitochondr ial membrane potential (Delta psi(m)). After mitochondrial loss of cytochro me c, rho(0) cells underwent little change in glutathione (GSH) redox poten tial whereas a dramatic oxidation in GSH/glutathione disulfide (GSSG) pool occurred in parental rho(+) cells. These results show that mitochondrial si gnaling of apoptosis via cytochrome c release was preserved in cells lackin g mtDNA. However, intracellular oxidation that normally accompanies apoptos is was lost, indicating that the mitochondrial respiratory chain provides t he major source of redox signaling in apoptosis.