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 machinery. However, cells that lack mitochondrial DNA (rho(0) cells) retain apparently normal apoptotic signaling. In the present study, we examined mitochondrial mechanisms of apoptosis in rho(0) osteosarcoma cells treated with s...

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Bibliographic Details
Published in:The Journal of biological chemistry 1999-10, Vol.274 (42), p.29905-29911
Main Authors: Jiang, S, Cai, J, Wallace, D C, Jones, D P
Format: Article
Language:English
Subjects:
Apoptosis - drug effects
Caspase 3
Caspases - metabolism
cytochrome c
Cytochrome c Group - metabolism
DNA, Mitochondrial - metabolism
Enzyme Activation
Glutathione - metabolism
glutathione disulfide
Oxidation-Reduction
Signal Transduction
staurosporine
Staurosporine - pharmacology
Tumor Cells, Cultured
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Summary:Mitochondria serve as a pivotal component of the apoptotic cell death machinery. However, cells that lack mitochondrial DNA (rho(0) cells) retain apparently normal apoptotic signaling. In the present study, we examined mitochondrial mechanisms of apoptosis in rho(0) osteosarcoma cells treated with staurosporine. Immunohistochemistry revealed that rho(0) cells maintained a normal cytochrome c distribution in mitochondria even though these cells were deficient in respiration. Upon staurosporine treatment, cytochrome c was released concomitantly with activation of caspase 3 and loss of mitochondrial membrane potential (Deltapsi(m)). After mitochondrial loss of cytochrome c, rho(0) cells underwent little change in glutathione (GSH) redox potential whereas a dramatic oxidation in GSH/glutathione disulfide (GSSG) pool occurred in parental rho(+) cells. These results show that mitochondrial signaling of apoptosis via cytochrome c release was preserved in cells lacking mtDNA. However, intracellular oxidation that normally accompanies apoptosis was lost, indicating that the mitochondrial respiratory chain provides the major source of redox signaling in apoptosis.
ISSN:0021-9258
DOI:10.1074/jbc.274.42.29905