Superoxide in Apoptosis
MITOCHONDRIAL GENERATION TRIGGERED BY CYTOCHROMEc LOSS*
Abstract
Activation of apoptosis is associated with generation of reactive oxygen species. The present research shows that superoxide is produced by mitochondria isolated from apoptotic cells due to a switch from the normal 4-electron reduction of O2 to a 1-electron reduction when cytochromec is released from mitochondria. Bcl-2, a protein that protects against apoptosis and blocks cytochrome c release, prevents superoxide production when it is overexpressed. The switch in electron transfer provides a mechanism for redox signaling that is concomitant with cytochrome c-dependent activation of caspases. The block of cytochrome c release provides a mechanism for the apparent antioxidant function of Bcl-2.
Footnotes
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↵* This work was supported by National Institutes of Health Grants ES 09047 and EY 07892.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵‡ To whom correspondence should be addressed. Tel.: 404-727-5970; Fax: 404-727-3231; E-mail: dpjones{at}emory.edu.
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↵1 The abbreviations used are: ROS, reactive oxygen species; cyt c, cytochrome c; SOD, superoxide dismutase; NAC, N-acetylcysteine; TNF, tumor necrosis factor; MnSOD, manganese superoxide dismutase; DHR, dihydrorhodamine;Eh, GSH redox potential; MPT, mitochondrial permeability transition.
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- Received December 16, 1997.
- Revision received February 24, 1998.
- The American Society for Biochemistry and Molecular Biology, Inc.
