Minimalist Model Systems Reveal Similarities and Differences between Membrane Interaction Modes of MCL1 and BAK

Landeta, Olatz; Landajuela, Ane; García‐Sáez, Ana J.; Basáñez, Gorka

doi:10.1074/jbc.m114.602193

Cited by 10 publications

(4 citation statements)

References 46 publications

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“…These sites can then be entry points for BAX and BAK insertion, which agrees with the fact that CL and Ca 2+ have been shown to facilitate BAX insertion, oligomerization, and membrane permeabilization [232,[244][245][246][247][248]. CL has also been shown to promote membrane targeting of BCL-X L , as well as MCL-1 and BAK, when using small unilamellar vesicles, supraphysiological concentrations of CL or when combined with BID [249,250]. Once recruited, molecular dynamic simulations suggest that CL might also regulate the function of BCL-X L through exposure of its BH3-binding pocket [251].…”

Section: Cardiolipinsupporting

confidence: 70%

Balancing life and death: BCL‐2 family members at diverse ER–mitochondrial contact sites

Means

Katz

2021

The FEBS Journal

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The outer mitochondrial membrane is a busy place. One essential activity for cellular survival is the regulation of membrane integrity by the BCL‐2 family of proteins. Another critical facet of the outer mitochondrial membrane is its close approximation with the endoplasmic reticulum. These mitochondrial‐associated membranes (MAMs) occupy a significant fraction of the mitochondrial surface and serve as key signaling hubs for multiple cellular processes. Each of these pathways may be considered as forming their own specialized MAM subtype. Interestingly, like membrane permeabilization, most of these pathways play critical roles in regulating cellular survival and death. Recently, the pro‐apoptotic BCL‐2 family member BOK has been found within MAMs where it plays important roles in their structure and function. This has led to a greater appreciation that multiple BCL‐2 family proteins, which are known to participate in numerous functions throughout the cell, also have roles within MAMs. In this review, we evaluate several MAM subsets, their role in cellular homeostasis, and the contribution of BCL‐2 family members to their functions.

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Section: Cardiolipinsupporting

confidence: 70%

Balancing life and death: BCL‐2 family members at diverse ER–mitochondrial contact sites

Means

Katz

2021

The FEBS Journal

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“…Other than its role in BAX and BAK activation, the OMM also has a critical role in the interaction of active BAX and BAK with prosurvival BCL-2 proteins. 109 , 110 , 111 Known as the 'retrotranslocation' theory, it has been shown that cytosolic BAX and BAK spontaneously attach to the OMM, which promotes their homodimerization and MOMP, unless prosurvival members are present to heterodimerize with them at the OMM and cause their retrotranslocation into the cytosol. 112 , 113 Thus, it is thought that in healthy cells BAX and BAK are retained in the cytosol or continuously retrotranslocated by prosurvival proteins to avoid MOMP.…”

Section: Bcl-2 Family Effectors: How To Permeabilize the Ommmentioning

confidence: 99%

MOMP, cell suicide as a BCL-2 family business

2017

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Apoptosis shapes development and differentiation, has a key role in tissue homeostasis, and is deregulated in cancer. In most cases, successful apoptosis is triggered by mitochondrial outer membrane permeabilization (MOMP), which defines the mitochondrial or intrinsic pathway and ultimately leads to caspase activation and protein substrate cleavage. The mitochondrial apoptotic pathway centered on MOMP is controlled by an intricate network of events that determine the balance of the cell fate choice between survival and death. Here we will review how MOMP proceeds and how the main effectors cytochrome c, a heme protein that has a crucial role in respiration, and second mitochondria-derived activator of caspase (SMAC), as well as other intermembrane space proteins, orchestrate caspase activation. Moreover, we discuss recent insights on the interplay of the upstream coordinators and initiators of MOMP, the BCL-2 family. This review highlights how our increasing knowledge on the regulation of critical checkpoints of apoptosis integrates with understanding of cancer development and has begun to translate into therapeutic clinical benefit.

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“…In the case of GSDMs, it seems that arcs are intermediates transitioning into complete rings in which lipids are excluded. However, the BAX/BAK pores are flexible and dynamic, and their size depends on protein density at the membrane and on lipid composition (Landeta et al , 2011; Bleicken et al , 2013; Landeta et al , 2015; Subburaj et al , 2015; Salvador‐Gallego et al , 2016; Cosentino & Garcia‐Saez, 2017). This, together with the difficulty to define interaction surfaces between BAX/BAK dimers, supports a model in which protein dimers and lipids could be intermixed with each other also in the ring‐like structures.…”

Section: Pore Formation In Membranes Is a Conserved Strategy To Kill mentioning

confidence: 99%

Pore formation in regulated cell death

2020

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The discovery of alternative signaling pathways that regulate cell death has revealed multiple strategies for promoting cell death with diverse consequences at the tissue and organism level. Despite the divergence in the molecular components involved, membrane permeabilization is a common theme in the execution of regulated cell death. In apoptosis, the permeabilization of the outer mitochondrial membrane by BAX and BAK releases apoptotic factors that initiate the caspase cascade and is considered the point of no return in cell death commitment. Pyroptosis and necroptosis also require the perforation of the plasma membrane at the execution step, which involves Gasdermins in pyroptosis, and MLKL in the case of necroptosis. Although BAX/BAK, Gasdermins and MLKL share certain molecular features like oligomerization, they form pores in different cellular membranes via distinct mechanisms. Here, we compare and contrast how BAX/BAK, Gasdermins, and MLKL alter membrane permeability from a structural and biophysical perspective and discuss the general principles of membrane permeabilization in the execution of regulated cell death.

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Minimalist Model Systems Reveal Similarities and Differences between Membrane Interaction Modes of MCL1 and BAK

Cited by 10 publications

References 46 publications

Balancing life and death: BCL‐2 family members at diverse ER–mitochondrial contact sites

Balancing life and death: BCL‐2 family members at diverse ER–mitochondrial contact sites

MOMP, cell suicide as a BCL-2 family business

Pore formation in regulated cell death

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