Cytochrome c deficiency causes embryonic lethality and attenuates stress-induced apoptosis.
Cytochrome c released from mitochondria has been proposed to be an essential component of an apoptotic pathway responsive to DNA damage and other forms of cell stress. Murine embryos devoid of cytochrome c die in utero by midgestation, but cell lines established from early cytochrome c null embryos are viable under conditions that compensate for defective oxidative phosphorylation. As compared to cell lines established from wild-type embryos, cells lacking cytochrome c show reduced caspase-3 activation and are resistant to the proapoptotic effects of UV irradiation, serum withdrawal, or staurosporine. In contrast, cells lacking cytochrome c demonstrate increased sensitivity to cell death signals triggered by TNFalpha. These results define the role of cytochrome c in different apoptotic signaling cascades.
Li
K
K
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75390, USA.
Li
Y
Y
Shelton
J M
JM
Richardson
J A
JA
Spencer
E
E
Chen
Z J
ZJ
Wang
X
X
Williams
R S
RS
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D003574:Cytochrome c Group / Q000172:deficiency* / Q000235:genetics; D020964:Embryo Loss; D004622:Embryo, Mammalian / Q000378:metabolism* / Q000473:pathology*; D005314:Embryonic and Fetal Development / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D051379:Mice
D003574:Cytochrome c Group