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Bad is essential for Bcl-xL-enhanced Bax shuttling between mitochondria and cytosol.
- Source :
-
The international journal of biochemistry & cell biology [Int J Biochem Cell Biol] 2023 Feb; Vol. 155, pp. 106359. Date of Electronic Publication: 2022 Dec 29. - Publication Year :
- 2023
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Abstract
- Although Bcl-xL has been shown to retrotranslocate Bax from mitochondria to cytosol, other studies have found that Bcl-xL also stabilizes the mitochondrial localization of Bax. It is still unclear what causes the difference in Bcl-xL-regulated Bax localization. Bad, a BH3-only protein with a high affinity for Bcl-xL, may play an important role in Bcl-xL-regulated Bax shuttling. Here, we found that Bcl-xL enhanced both translocalization and retrotranslocation of mitochondrial Bax, as evidenced by quantitative co-localization, western blots and fluorescence loss in photobleaching (FLIP) analyses. Notably, Bad knockdown prevented Bcl-xL-mediated Bax retrotranslocation, indicating Bad was essential for this process. Quantitative fluorescence resonance energy transfer (FRET) imaging in living cells and co-immunoprecipitation analyses showed that the interaction of Bcl-xL with Bad was stronger than that with Bax. The Bad mimetic ABT-737 dissociated Bax from Bcl-xL on isolated mitochondria, suggesting that mitochondrial Bax was directly liberated to cytosol due to Bad binding to Bcl-xL. In addition, MK-2206, an Akt inhibitor, decreased Bad phosphorylation while increasing cytosolic Bax proportion. Our data firmly demonstrate a notion that Bad binds to mitochondrial Bcl-xL to release Bax, resulting in retrotranslocation of Bax to cytosol, and that the amount of Bad involved is regulated by Akt signaling.<br />Competing Interests: Declaration of Competing Interest The authors have no relevant financial or non-financial interests to disclose.<br /> (Copyright © 2023 Elsevier Ltd. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1878-5875
- Volume :
- 155
- Database :
- MEDLINE
- Journal :
- The international journal of biochemistry & cell biology
- Publication Type :
- Academic Journal
- Accession number :
- 36586532
- Full Text :
- https://doi.org/10.1016/j.biocel.2022.106359