ArticleThe Journal of biological chemistry2011
Reconstitution of proapoptotic BAK function in liposomes reveals a dual role for mitochondrial lipids in the BAK-driven membrane permeabilization process.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 68 citations in OpenAlex.
- Apoptosis Regulation in Osteoarthritis and the Influence of Lipid Interactions.International journal of molecular sciences · 2023Review
- Structural basis for proapoptotic activation of Bak by the noncanonical BH3-only protein Pxt1.PLoS biology · 2023Article
- Apoptotic mitochondrial poration by a growing list of pore-forming BCL-2 family proteins.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Article
- Visualization of BOK pores independent of BAX and BAK reveals a similar mechanism with differing regulation.Cell death and differentiation · 2023Article
- LC3 subfamily in cardiolipin-mediated mitophagy: a comparison of the LC3A, LC3B and LC3C homologs.Autophagy · 2022Article
- Disruption of mitochondrial quality control genes promotes caspase-resistant cell survival following apoptotic stimuli.The Journal of biological chemistry · 2022Article
- High-resolution analysis of the conformational transition of pro-apoptotic Bak at the lipid membrane.The EMBO journal · 2021Article
- Pore formation in regulated cell death.The EMBO journal · 2020Review
- The Incomplete Puzzle of the BCL2 Proteins.Cells · 2019Review
- NME4/nucleoside diphosphate kinase D in cardiolipin signaling and mitophagy.Laboratory investigation; a journal of technical methods and pathology · 2018Review
- MOMP, cell suicide as a BCL-2 family business.Cell death and differentiation · 2018Review
- Apoptotic foci at mitochondria: in and around Bax pores.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2017Review
- Pore formation by dimeric Bak and Bax: an unusual pore?Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2017Review
- Bax and Bak Pores: Are We Closing the Circle?Trends in cell biology · 2017Review
- Mitochondria, cholesterol and cancer cell metabolism.Clinical and translational medicine · 2016Review
- Biguanides sensitize leukemia cells to ABT-737-induced apoptosis by inhibiting mitochondrial electron transport.Oncotarget · 2016Article
- The deadly landscape of pro-apoptotic BCL-2 proteins in the outer mitochondrial membrane.The FEBS journal · 2016Review
- cBid, Bax and Bcl-xL exhibit opposite membrane remodeling activities.Cell death & disease · 2016Article
- Minimalist Model Systems Reveal Similarities and Differences between Membrane Interaction Modes of MCL1 and BAK.The Journal of biological chemistry · 2015Article
- Emerging understanding of Bcl-2 biology: Implications for neoplastic progression and treatment.Biochimica et biophysica acta · 2015Review
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BAK is a key effector of mitochondrial outer membrane permeabilization (MOMP) whose molecular mechanism of action remains to be fully dissected in intact cells, mainly due to the inherent complexity of the intracellular apoptotic machinery. Here we show that the core features of the BAK-driven MOMP pathway can be reproduced in a highly simplified in vitro system consisting of recombinant human BAK lacking the carboxyl-terminal 21 residues (BAKΔC) and tBID in combination with liposomes bearing an appropriate lipid environment. Using this minimalist reconstituted system we established that tBID suffices to trigger BAKΔC membrane insertion, oligomerization, and pore formation. Furthermore, we demonstrate that tBID-activated BAKΔC permeabilizes the membrane by forming structurally dynamic pores rather than a large proteinaceous channel of fixed size. We also identified two distinct roles played by mitochondrial lipids along the molecular pathway of BAKΔC-induced membrane permeabilization. First, using several independent approaches, we showed that cardiolipin directly interacts with BAKΔC, leading to a localized structural rearrangement in the protein that "primes" BAKΔC for interaction with tBID. Second, we provide evidence that selected curvature-inducing lipids present in mitochondrial membranes specifically modulate the energetic expenditure required to create the BAKΔC pore. Collectively, our results support the notion that BAK functions as a direct effector of MOMP akin to BAX and also adds significantly to the growing evidence indicating that mitochondrial membrane lipids are actively implicated in BCL-2 protein family function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.