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| Mitochondrial cytochrome c release in apoptosis occurs upstream of DEVD-specific caspase activation and independently of mitochondrial transmembrane depolarization |
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| Author(s): Bossy-Wetzel E, Newmeyer DD, Green DR |
| Source: EMBO JOURNAL Volume: 17 Issue: 1 Pages: 37-49 Published: JAN 2 1998 |
| Times Cited: 874 References: 106 |
| Abstract: Mitochondrial cytochrome c, which functions as an electron carrier in the respiratory chain, translocates to the cytosol in cells undergoing apoptosis, where it participates in the activation of DEVD-specific caspases. The apoptosis inhibitors Bcl-2 or Bcl-x(L) prevent the efflux of cytochrome c from mitochondria. The mechanism responsible for the release of cytochrome c from mitochondria during apoptosis is unknown. Here, we report that cytochrome c release from mitochondria is an early event in the apoptotic process induced by UVB irradiation or staurosporine treatment in CEM or HeLa cells, preceding or at the time of DEVD-specific caspase activation and substrate cleavage. A reduction in mitochondrial transmembrane potential (Delta psi) occurred considerably later than cytochrome c translocation and caspase activation, and was not necessary for DNA fragmentation. Although zVAD-fmk substantially blocked caspase activity, a reduction in Delta psi(m) and cell death, it faded to prevent the passage of cytochrome c from mitochondria to the cytosol. Thus the translocation of cytochrome c from mitochondria to cytosol does not require a mitochondrial transmembrane depolarization. |
| Document Type: Review |
| Language: English |
| Reprint Address: Green, DR (reprint author), La Jolla Inst Allergy & Immunol, Div Cellular Immunol, 10355 Sci Ctr Dr, San Diego, CA 92121 USA |
Addresses:
1. La Jolla Inst Allergy & Immunol, Div Cellular Immunol, San Diego, CA 92121 USA |
| Publisher: OXFORD UNIV PRESS, GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: YU347 |
| ISSN: 0261-4189 |
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