Alteration of tBiD-Induced Apoptotic Bax Poration in Mitochondrial Membranes by Mutations and Small Molecules
نویسندگان
چکیده
منابع مشابه
Bax oligomerization in mitochondrial membranes requires tBid (caspase-8-cleaved Bid) and a mitochondrial protein.
In response to various apoptotic stimuli, Bax, a pro-apoptotic member of the Bcl-2 family, is oligomerized and permeabilizes the mitochondrial outer membrane to apoptogenic factors, including cytochrome c. Bax oligomerization can also be induced by incubating isolated mitochondria containing endogenous Bax with recombinant tBid (caspase-8-cleaved Bid) in vitro. The mechanism by which Bax oligom...
متن کاملStepwise activation of BAX and BAK by tBID, BIM, and PUMA initiates mitochondrial apoptosis.
While activation of BAX/BAK by BH3-only molecules (BH3s) is essential for mitochondrial apoptosis, the underlying mechanisms remain unsettled. Here we demonstrate that BAX undergoes stepwise structural reorganization leading to mitochondrial targeting and homo-oligomerization. The alpha1 helix of BAX keeps the alpha9 helix engaged in the dimerization pocket, rendering BAX as a monomer in cytoso...
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The cellular response to p53 activation varies greatly in a stimulus- and cell type-specific manner. Dissecting the molecular mechanisms defining these cell fate choices will assist the development of effective p53-based cancer therapies and also illuminate fundamental processes by which gene networks control cellular behaviour. Using an experimental system wherein stimulus-specific p53 respons...
متن کاملA DR4:tBID axis drives the p53 apoptotic response by promoting oligomerisation of poised BAX
Thank you for submitting your manuscript for consideration by the EMBO Journal. It has now been seen by two referees whose comments are shown below. We share the referees' interest in this manuscript, but also felt at the editorial level that the dataset could be developed realistically to allow more general as well as more mechanistically developed conclusions. I outline below key points raise...
متن کاملThe mitochondrial TOM complex is required for tBid/Bax-induced cytochrome c release.
Cytochrome c release from mitochondria is a key event in apoptosis signaling that is regulated by Bcl-2 family proteins. Cleavage of the BH3-only protein Bid by multiple proteases leads to the formation of truncated Bid (tBid), which, in turn, promotes the oligomerization/insertion of Bax into the mitochondrial outer membrane and the resultant release of proteins residing in the intermembrane s...
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ژورنال
عنوان ژورنال: Biophysical Journal
سال: 2020
ISSN: 0006-3495
DOI: 10.1016/j.bpj.2019.11.1178