Application of cryo-electron microscopy for investigation of Bax-induced pores in apoptosis
Source abstract
Abstract
Abstract Mitochondrial outer membrane permeabilization (MOMP) is a critical step in apoptosis, the molecular mechanisms of which have been a subject of intensive study. This process is important for therapeutic intervention in various diseases, such as cancer. Pro-apoptotic Bax and Bak are functionally redundant and structurally homologous. When activated at the mitochondrial outer membrane, they cause the membrane to permeabilize and release apoptogenic proteins from the intermembrane space. To unravel the molecular mechanisms of this unique and important event, we systematically reduced the experimental system. Simple outer membrane vesicles and liposomes recapitulated many features of MOMP. Although conventional transmission electron microscopy could not detect any membrane changes during MOMP in these vesicles, cryo-electron microscopy successfully revealed Bax-induced delicate pores, owing to its ability to preserve native, hydrated membrane structure. The data are consistent with the idea that Bax is unfolded and embedded in the bilayer and deforms the membrane to form a large pore. Together with the biochemical and structure data in the literature, we now have more comprehensive models of the key function of Bax. We hope that new tools, such as lipid nanodiscs, will give us an atomic-level resolution and finally solve Bax structure in the membrane, where it functions.
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Research context
OpenAlex topics: RNA Interference and Gene Delivery · Lipid Membrane Structure and Behavior · Cell death mechanisms and regulation
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
1La Jolla Institute for Allergy and Immunology, 9420 Athena Circle La Jolla, CA 92037, USA
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