English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Lipid unsaturation promotes BAX and BAK pore activity during apoptosis

Dadsena, S., Cuevas Arenas, R., Vieira, G., Brodesser, S., Melo, M. N., & García-Sáez, A. J. (2024). Lipid unsaturation promotes BAX and BAK pore activity during apoptosis. Nature Communications, 15: 4700. doi:10.1038/s41467-024-49067-6.

Item is

Files

show Files
hide Files
:
s41467-024-49067-6.pdf (Any fulltext), 5MB
Name:
s41467-024-49067-6.pdf
Description:
-
OA-Status:
Not specified
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show

Creators

show
hide
 Creators:
Dadsena, Shashank1, Author
Cuevas Arenas, Rodrigo2, Author
Vieira, Gonçalo3, Author
Brodesser, Susanne4, Author
Melo, Manuel N.3, Author
García-Sáez, Ana J.1, 5, Author                 
Affiliations:
1Institute for Genetics, CECAD Research Center, University of Cologne, Cologne, Germany, ou_persistent22              
2Structural Biochemistry, Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, The Netherlands, ou_persistent22              
3Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal, ou_persistent22              
4Cluster of Excellence Cellular Stress Responses in Aging-associated Diseases (CECAD), Faculty of Medicine and University Hospital of Cologne, University of Cologne, Cologne, Germany, ou_persistent22              
5Department of Membrane Dynamics, Max Planck Institute of Biophysics, Max Planck Society, ou_3529759              

Content

show
hide
Free keywords: Animals, Apoptosis, bcl-2 Homologous Antagonist-Killer Protein, bcl-2-Associated X Protein, Cell Line, Tumor, Fatty Acids, Unsaturated, Humans, Mitochondria, Mitochondrial Membranes, Molecular Dynamics Simulation
 Abstract: BAX and BAK are proapoptotic members of the BCL2 family that directly mediate mitochondrial outer membrane permeabilition (MOMP), a central step in apoptosis execution. However, the molecular architecture of the mitochondrial apoptotic pore remains a key open question and especially little is known about the contribution of lipids to MOMP. By performing a comparative lipidomics analysis of the proximal membrane environment of BAK isolated in lipid nanodiscs, we find a significant enrichment of unsaturated species nearby BAK and BAX in apoptotic conditions. We then demonstrate that unsaturated lipids promote BAX pore activity in model membranes, isolated mitochondria and cellular systems, which is further supported by molecular dynamics simulations. Accordingly, the fatty acid desaturase FADS2 not only enhances apoptosis sensitivity, but also the activation of the cGAS/STING pathway downstream mtDNA release. The correlation of FADS2 levels with the sensitization to apoptosis of different lung and kidney cancer cell lines by co-treatment with unsaturated fatty acids supports the relevance of our findings. Altogether, our work provides an insight on how local lipid environment affects BAX and BAK function during apoptosis.

Details

show
hide
Language(s): eng - English
 Dates: 2023-07-072024-05-222024-06-03
 Publication Status: Issued
 Pages: 16
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1038/s41467-024-49067-6
BibTex Citekey: dadsena_lipid_2024
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Nature Communications
  Abbreviation : Nat. Commun.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 15 Sequence Number: 4700 Start / End Page: - Identifier: ISSN: 2041-1723
CoNE: https://pure.mpg.de/cone/journals/resource/2041-1723