Glutathione depletion causes cytochrome c release even in the absence of cell commitment to apoptosis

被引:119
作者
Ghibelli, L
Coppola, S
Fanelli, C
Rotilio, G
Civitareale, P
Scovassi, AI
Ciriolo, MR
机构
[1] Univ Roma Tor Vergata, Dipartimento Biol, I-00133 Rome, Italy
[2] CNR, Ist Genet Biochim & Evoluzionist, I-27100 Pavia, Italy
[3] Univ Chieti, Dipartimento Sci Biomed, I-66013 Chieti, Italy
关键词
caspase; 3; redox modulation; PARP; apoptotic cytochrome c release; puromycin;
D O I
10.1096/fasebj.13.14.2031
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We demonstrate here that the release of mature cytochrome c from mitochondria is a cellular response to the depletion of glutathione, the main intracellular antioxidant, independently from the destiny of the cells, i.e., apoptosis or survival. On the one hand, cytosolic cytochrome c was detected in cells where the inhibition of glutathione synthesis led to glutathione depletion without impairing viability or in tight concomitance with glutathione depletion prior to puromycin-induced apoptosis. Removal of the apoptogenic agent prior to apoptosis, but after glutathione extrusion and cytochrome c release, led to recovery of preapoptotic cells, which resume healthy features, i.e., restoration of normal glutathione levels and disappearance of cytosolic cytochrome c. On the other hand, in an example of apoptosis occurring without glutathione depletion, no translocation of cytochrome c from mitochondria to cytosol was detected. Unlike the other instances of apoptosis, in this case caspase 3 was not activated, thus suggesting the following oxidant-related apoptotic pathway: glutathione depletion, cytochrome c release, and caspase 3 activation. These results show that cytochrome c release is not a terminal event leading cells to apoptosis, but rather is the consequence of a redox disequilibrium that, under some circumstances, may be associated with apoptosis.-Ghibelli, L., Coppola, S., Fanelli, C., Rotilio, G., Civitareale, P., Scovassi, A. I., Ciriolo, M. R. Glutathione depletion causes cytochrome c release even in the absence of cell commitment to apoptosis.
引用
收藏
页码:2031 / 2036
页数:6
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