Bcl-xL inhibits tBid and Bax <i>via</i> distinct mechanisms

Murad, Fabronia; García‐Sáez, Ana J.

doi:10.1039/d0fd00045k

Cited by 8 publications

(4 citation statements)

References 42 publications

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“…Indeed what stands out in the tBid/Bax interaction model inspired by our experiments ( Figure 8 c) is that the interaction between tBid and Bax seems designed to pull Bax down and anchors it in the membrane, maybe just long enough for Bax to become activated by the membrane, and maybe greatly accelerating a process which may happen in the absence of tBid, but would be much slower. This formalizes an already existing narrative for the tBid/Bax interaction, which is that tBid “recruits” Bax to the membrane, and can shift the equilibrium between the soluble and membrane forms of Bax [ 22 , 23 , 24 , 75 ].…”

Section: Discussionmentioning

confidence: 91%

Direct Measurement of the Affinity between tBid and Bax in a Mitochondria-Like Membrane

Rose

Kurylowicz

Mahmood

et al. 2021

IJMS

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The execution step in apoptosis is the permeabilization of the outer mitochondrial membrane, controlled by Bcl-2 family proteins. The physical interactions between the different proteins in this family and their relative abundance literally determine the fate of the cells. These interactions, however, are difficult to quantify, as they occur in a lipid membrane and involve proteins with multiple conformations and stoichiometries which can exist both in soluble and membrane. Here we focus on the interaction between two core Bcl-2 family members, the executor pore-forming protein Bax and the truncated form of the activator protein Bid (tBid), which we imaged at the single particle level in a mitochondria-like planar supported lipid bilayer. We inferred the conformation of the proteins from their mobility, and detected their transient interactions using a novel single particle cross-correlation analysis. We show that both tBid and Bax have at least two different conformations at the membrane, and that their affinity for one another increases by one order of magnitude (with a 2D-KD decreasing from ≃1.6/m2 to ≃0.1/m2) when they pass from their loosely membrane-associated to their transmembrane form. We conclude by proposing an updated molecular model for the activation of Bax by tBid.

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Section: Discussionmentioning

confidence: 91%

Direct Measurement of the Affinity between tBid and Bax in a Mitochondria-Like Membrane

Rose

Kurylowicz

Mahmood

et al. 2021

IJMS

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“…The interaction between anti-apoptotic and pro-apoptotic BCL-2 family proteins can directly determine the fate of different cardiac pathological processes, including myocardial infarction, dilated cardiomyopathy, and ischemic heart disease [49]. For example, BCL-2 can signi cantly reduce the infarct size caused by apoptosis [16,50], while BCL-xL can inhibit the expression of the pro-apoptotic molecules Bax and Bid through different mechanisms [51]. Our results showed that decreased NRF-1 expression caused the expression of the anti-apoptotic molecules BCL-2 and BCL-xL to decrease, while that of the pro-apoptotic molecule Bax was not affected.…”

Section: Discussionmentioning

confidence: 99%

Effects of NRF-1 and PGC-1α Cooperation on HIF-1α and Rat Cardiomyocyte Apoptosis Under Hypoxia

Niu

et al. 2021

Preprint

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Hypoxia is a primary inducer of cardiomyocyte injury, its significant marker being hypoxia-induced cardiomyocyte apoptosis. Nuclear respiratory factor-1 (NRF-1) and hypoxia-inducible factor (HIF)-1α are transcriptional regulatory elements implicated in multiple biological functions, including oxidative stress response. However, their roles in hypoxia-induced cardiomyocyte apoptosis remain unknown. The effect HIF-α, together with NRF-1, exerts on cardiomyocyte apoptosis also remains unclear. We established a myocardial hypoxia model and investigated the effects of these proteins on the proliferation and apoptosis of rat cardiomyocytes (H9C2) under hypoxia. Further, we examined the association between NRF-1 and HIF-1α to improve the current understanding of NRF-1 anti-apoptotic mechanisms. The results showed that NRF-1 and HIF-1α are important anti-apoptotic molecules in H9C2 cells under hypoxia, although their regulatory mechanisms differ. NRF-1 could bind to the promoter region of Hif-1α and negatively regulate its expression. Additionally, HIF-1β exhibited competitive binding with NRF-1 and HIF-1α, demonstrating a synergism between NRF-1 and the peroxisome proliferator-activated receptor-gamma coactivator-1α. These results indicate that cardiomyocytes can regulate different molecular patterns to tolerate hypoxia, providing a novel methodological framework for studying cardiomyocyte apoptosis under hypoxia.

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“…Various forms of endothelial death, such as apoptosis [42], pyroptosis [43], and autophagy [44], can influence the development and progression of atherosclerosis. First, salidroside upregulates the expression of B-cell lymphomaextra large (Bcl-xL), an antiapoptotic protein, and inhibits Ox-LDL-induced EC apoptosis [45]. Zhang et al [46] used human coronary artery endothelial cell (HCAECs) to analyze the effect of salidroside (100 µM, 24 h) on EC apoptosis.…”

Section: Effects Of Salidroside On Ec Deathmentioning

confidence: 99%

Antiatherosclerotic Effect and Molecular Mechanism of Salidroside

Fei¹,

Tong²,

Jia³

2023

Rev. Cardiovasc. Med.

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Atherosclerotic cardiovascular disease is currently the leading cause of death worldwide. Its pathophysiological basis includes endothelial dysfunction, macrophage activation, vascular smooth muscle cell (VSMC) proliferation, lipid metabolism, platelet aggregation, and changes in the gut microbiota. Salidroside has beneficial effects on atherosclerosis through multiple pathways. In this review, we present studies on the regulatory effect of salidroside on atherosclerosis. Furthermore, we report the protective effects of salidroside against atherosclerosis by ameliorating endothelial dysfunction, suppressing macrophage activation and polarization, inhibiting VSMC proliferation, adjusting lipid metabolism, attenuating platelet aggregation, and modulating the gut microbiota. This review provides further understanding of the molecular mechanism of salidroside and new ideas for atherosclerosis management.

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Bcl-xL inhibits tBid and Bax via distinct mechanisms

Abstract:
The proteins of the Bcl-2 family are key regulators of apoptosis. They form a complex interaction network in the cytosol and in the cellular membranes, whose outcome determines mitochondrial permeabilization...

Cited by 8 publications

References 42 publications

Direct Measurement of the Affinity between tBid and Bax in a Mitochondria-Like Membrane

Direct Measurement of the Affinity between tBid and Bax in a Mitochondria-Like Membrane

Effects of NRF-1 and PGC-1α Cooperation on HIF-1α and Rat Cardiomyocyte Apoptosis Under Hypoxia

Antiatherosclerotic Effect and Molecular Mechanism of Salidroside

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Bcl-xL inhibits tBid and Bax via distinct mechanisms

Abstract: The proteins of the Bcl-2 family are key regulators of apoptosis. They form a complex interaction network in the cytosol and in the cellular membranes, whose outcome determines mitochondrial permeabilization...

Cited by 8 publications

References 42 publications

Direct Measurement of the Affinity between tBid and Bax in a Mitochondria-Like Membrane

Direct Measurement of the Affinity between tBid and Bax in a Mitochondria-Like Membrane

Effects of NRF-1 and PGC-1α Cooperation on HIF-1α and Rat Cardiomyocyte Apoptosis Under Hypoxia

Antiatherosclerotic Effect and Molecular Mechanism of Salidroside

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Product

Resources

About

Abstract:
The proteins of the Bcl-2 family are key regulators of apoptosis. They form a complex interaction network in the cytosol and in the cellular membranes, whose outcome determines mitochondrial permeabilization...