TY - JOUR
T1 - Cytochrome c deficiency causes embryonic lethality and attenuates stress-induced apoptosis
AU - Li, Kang
AU - Li, Yucheng
AU - Shelton, John M.
AU - Richardson, James A.
AU - Spencer, Erika
AU - Chen, Zhijian J.
AU - Wang, Xiaodong
AU - Williams, R. Sanders
N1 - Funding Information:
We thank Dr. Kathy Graves and Zhao-Hui Xiong for help in generating transgenic mice, Jeff Stark for embryo sectioning, Dr. Min Fang for technical support, Drs. Anirban Maitra and Adi F. Gazdar for laser capture microdissection, and Drs. Michael Brown, Joseph Goldstein, and Rhonda Bassel-Duby for critical reading of the manuscript. This work was supported in part by grants from the National Institutes of Health, the Welch Foundation, and the D. W. Reynolds Foundation.
PY - 2000/5/12
Y1 - 2000/5/12
N2 - 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 TNFα. These results define the role of cytochrome c in different apoptotic signaling cascades.
AB - 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 TNFα. These results define the role of cytochrome c in different apoptotic signaling cascades.
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U2 - 10.1016/S0092-8674(00)80849-1
DO - 10.1016/S0092-8674(00)80849-1
M3 - Article
C2 - 10830166
AN - SCOPUS:0034640102
SN - 0092-8674
VL - 101
SP - 389
EP - 399
JO - Cell
JF - Cell
IS - 4
ER -