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| Intracellular ATP levels determine cell death fate by apoptosis or necrosis |
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| Author(s): Eguchi Y, Shimizu S, Tsujimoto Y |
| Source: CANCER RESEARCH Volume: 57 Issue: 10 Pages: 1835-1840 Published: MAY 15 1997 |
| Times Cited: 599 References: 32 |
| Abstract: Although apoptosis and necrosis are morphologically distinct manifestations of cell death, apoptosis and some necroses share common features in the death signaling pathway involving functional steps of death-driving interleukin 1 beta-converting enzyme family proteases and anti-cell death protein Bcl-2. One evident physiological difference in cells undergoing apoptosis versus necrosis is in intracellular levels of ATP, In this study, me specifically addressed the question of whether apoptosis depends on intracellular ATP levels, since longer incubation under ATP-depleting conditions results in necrotic cell death, Incubation of cells in glucose-free medium with an inhibitor of mitochondrial F0F1-ATPases reduces intracellular ATP levels and completely blocks Fas/Apo-1-stimulated apoptosis, ATP supplied through glycolysis or oxidative phosphorylation restores the apoptotic cell death pathway. ATP depletion also leads to a block in Fas-induced activation of CPP32/Yama(-like) proteases, and when ATP is depleted after the activation of the proteases, subsequent apoptosis is significantly blocked, Thus, ATP-dependent steps exist both upstream and downstream of CPP32/Yama(-like) protease activation in apoptotic signal transduction. Treatment with the calcium ionophore induces apoptosis under ATP-supplying conditions but induces necrotic cell death under ATP-depleting conditions, indicating that ATP levels are a determinant of manifestation of cell death. |
| Document Type: Article |
| Language: English |
Addresses:
1. OSAKA UNIV, SCH MED, CTR BIOMED RES, DEPT MED GENET, SUITA, OSAKA 565 JAPAN |
| Publisher: AMER ASSOC CANCER RESEARCH, PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 |
| Subject Category: Oncology |
| IDS Number: WZ216 |
| ISSN: 0008-5472 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |