Cytochrome c Deficiency Causes Embryonic Lethality and Attenuates Stress-Induced Apoptosis

Abstract

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.

Bax and Bcl-xL independently regulate apoptotic changes of yeast mitochondria that require VDAC but not adenine nucleotide translocator

“…The remaining samples were centrifuged, and aliquots (20 ml) of the supernatants were analysed by Western blotting using anti-yeast cytochrome c antibody (f).`T' represents an equivalent aliquot of mitochondria. Data are representative of three independent experiments example, cytochrome c plays an essential role in apoptosis in mammalian cell (Li et al, 2000), whereas it is not involved in yeast death induced by Bax (Gross et al, 2000). However, yeast mitochondria show apoptotic changes in response to Bcl-2 family of proteins in a similar way as mammalian mitochondria (Shimizu et al, 1999;Priault et al, 1999a, and this study).…”

Functional characterization of mitochondria in neutrophils: a role restricted to apoptosis

“…The fact that, in cytochrome c À/À cells, stress-induced apoptosis (i.e. the intrinsic death pathway) is attenuated but not abrogated, 37 suggests the existence of additional mechanisms, which are cytochrome cindependent and can mediate the intrinsic activation of caspases. Capsase-9 processing and activity has not been studied in the cytochrome c À/À cells, 37 but a cell-free system of endoplasmic reticulum stress-induced apoptosis, lacking cytochrome c and Apaf-1, has reportedly been capable of caspase-9 cleavage.…”

The p53-inducible apoptotic protein AMID is not required for normal development and tumor suppression

“…These death factors activate caspases through distinct mechanisms and eventually lead to apoptosis. In addition to the classic apoptotic pathways, studies have demonstrated that cytochrome c-, Apaf-1-, or caspases-deficient cells can still undergo apoptosis (Kuida et al, 1996;Cecconi et al, 1998;Hakem et al, 1998;Yoshida et al, 1998;Li et al, 2000). In addition, apoptosis induced by some stimuli cannot be inhibited by the pan-caspase inhibitor z-VAD-fmk (Amarante-Mendes et al, 1998;Bidere and Senik, 2001).…”