DOI: 10.1073/pnas.95.4.1455. Bcl-2 prevents apoptotic mitochondrial dysfunction by regulating proton flux

Bcl-2 prevents apoptotic mitochondrial dysfunction by regulating proton flux

10.1073/pnas.95.4.1455

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

We and others have recently shown that loss of the mitochondrial membrane potential (Δψ) precedes apoptosis and chemical-hypoxia-induced necrosis and is prevented by Bcl-2. In this report, we examine the biochemical mechanism used by Bcl-2 to prevent Δψ loss, as determined with mitochondria isolated from a cell line overexpressing human Bcl-2 or from livers of Bcl-2 transgenic mice. Although Bcl-2 had no effect on the respiration rate of isolated mitochondria, it prevented both Δψ loss and the permeability transition (PT) induced by various reagents, including Ca 2+ , H 2 O 2 , and tert -butyl hydroperoxide. Even under conditions that did not allow PT, Bcl-2 maintained Δψ, suggesting that the functional target of Bcl-2 is regulation of Δψ but not PT. Bcl-2 also maintained Δψ in the presence of the protonophore SF6847, which induces proton influx, suggesting that Bcl-2 regulates ion transport to maintain Δψ. Although treatment with SF6847 in the absence of Ca 2+ caused massive H + influx in control mitochondria, the presence of Bcl-2 induced H + efflux after transient H + influx. In this case, Bcl-2 did not enhance K + efflux. Furthermore, Bcl-2 enhanced H + efflux but not K + flux after treatment of mitochondria with Ca 2+ or tert -butyl hydroperoxide. These results suggest that Bcl-2 maintains Δψ by enhancing H + efflux in the presence of Δψ-loss-inducing stimuli.

Bibliography

Shimizu, S., Eguchi, Y., Kamiike, W., Funahashi, Y., Mignon, A., Lacronique, V., Matsuda, H., & Tsujimoto, Y. (1998). Bcl-2 prevents apoptotic mitochondrial dysfunction by regulating protonâflux. Proceedings of the National Academy of Sciences, 95(4), 1455â1459.

Authors 8

Shigeomi Shimizu (first)
Yutaka Eguchi (additional)
Wataru Kamiike (additional)
Yoshimitsu Funahashi (additional)
Alexandre Mignon (additional)
Virginia Lacronique (additional)
Hikaru Matsuda (additional)
Yoshihide Tsujimoto (additional)

References 39 Referenced 331

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:35 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 4:51 p.m.)
Indexed	3 weeks, 6 days ago (Aug. 2, 2025, 1:18 a.m.)
Issued	27 years, 6 months ago (Feb. 17, 1998)
Published	27 years, 6 months ago (Feb. 17, 1998)
Published Online	27 years, 6 months ago (Feb. 17, 1998)
Published Print	27 years, 6 months ago (Feb. 17, 1998)

Funders 0

None

BibTeX

@article{Shimizu_1998, title={Bcl-2 prevents apoptotic mitochondrial dysfunction by regulating proton flux}, volume={95}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.95.4.1455}, DOI={10.1073/pnas.95.4.1455}, number={4}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Shimizu, Shigeomi and Eguchi, Yutaka and Kamiike, Wataru and Funahashi, Yoshimitsu and Mignon, Alexandre and Lacronique, Virginia and Matsuda, Hikaru and Tsujimoto, Yoshihide}, year={1998}, month=feb, pages={1455–1459} }

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