02月 2, 2008 at 8:49 pm | Apoptosis & Mitochondria
- Posted by qixinming |
J. Biol. Chem., Vol. 283, Issue 6, 3476-3486, February 8, 2008
The role of the mitochondrial permeability transition (MPT) in apoptosis and necrosis is controversial. Here we show that the MPT regulates the release of cytochrome c for apoptosis during endoplasmic reticulum (ER) stress by remodeling the cristae junction (CJ). CEM cells, HCT116 colon cancer cells, and murine embryo fibroblast cells were treated with the ER stressor thapsigargin (THG), which led to cyclophilin D-dependent mitochondrial release of the profusion GTPase optic atrophy 1 (OPA1), which controls CJ integrity, and cytochrome c, leading to apoptosis. Interference RNA knockdown of Bax blocked OPA1 and cytochrome c release after THG treatment but did not prevent the MPT, showing that Bax was essential for the release of cytochrome c by MPT. In isolated mitochondria, MPT led to OPA1 and cytochrome c release independently of voltage-dependent anion channel and the outer membrane, indicating that the MPT is an inner membrane phenomenon. Last, the MPT was regulated by the electron transport chain but not mitochondrial reactive oxygen species, since THG-induced cell death was not blocked by antioxidants and did not occur in cells lacking mitochondrial DNA. Our results show that the MPT regulates CJ remodeling for cytochrome c-dependent apoptosis induced by ER stress and that mitochondrial electron transport is indispensable for this process.
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12月 22, 2007 at 10:46 am | Apoptosis & Mitochondria
- Posted by qixinming |
| J. Biol. Chem., Vol. 282, Issue 52, 37303-37307, December 28, 2007 |
Synergistic Inhibition of Mitochondrial Respiration by Anticancer Agent Erucylphosphohomocholine and Cyclosporin A* |
| significantly decreased ATP synthesis in isolated rat liver mitochondria at a concentration of 50 |
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12月 20, 2007 at 4:23 pm | Apoptosis & Mitochondria
- Posted by qixinming |
| Chemistry and Biology, Vol 14, 1204-1206, 26 November 2007 |
| Hsp90 Inhibitors Disrupt Mitochondrial Homeostasis in Cancer Cells |
| Hsp90 is a cytosolic molecular chaperone whose paralog in mitochondria, TRAP1, protects cells from oxidative stress. The recent study in Cell by Kang et |
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12月 20, 2007 at 3:39 pm | Apoptosis & Mitochondria
- Posted by qixinming |
| Cell Death and Differentiation advance online publication 14 |
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12月 3, 2007 at 4:18 pm | Apoptosis & Mitochondria
- Posted by qixinming |
| Molecular Cell, Vol 28, 624-637, 30 November 2007 |
| Nonapoptotic Role for Apaf-1 in the DNA Damage Checkpoint |
| Knockdown of Apaf-1 in human cells, knockout of apaf-1 in mice, and loss-of-function mutations in the Caenorhabditis elegans apaf-1 homolog ced-4 reveal the implication of Apaf-1/CED-4 in DNA damage-induced cell-cycle arrest. Apaf-1 loss compromised the DNA damage checkpoints elicited by ionizing irradiation or chemotherapy. Apaf-1 depletion reduced the activation of the checkpoint kinase Chk1 provoked by DNA damage, and knockdown of Chk1 abrogated the Apaf-1-mediated cell-cycle arrest. |
| uggesting that this pathway is clinically relevant. Hence, Apaf-1 exerts two distinct, phylogenetically conserved roles in response to mitochondrial |
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