Summary of project PR001935
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001935. The data can be accessed directly via it's Project DOI: 10.21228/M8M430 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001935 |
| Project DOI: | doi: 10.21228/M8M430 |
| Project Title: | Lipid unsaturation promotes BAX and BAK pore activity during apoptosis |
| Project Summary: | BAX and BAK are proapoptotic members of the BCL2 family that directly mediate mitochondrial outer membrane permeabilization (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 new insight on how local lipid environment affects BAX and BAK function during apoptosis. |
| Institute: | University of Cologne |
| Department: | Institute for Genetics, Cluster of Excellence Cellular Stress Responses in Aging-associated Diseases (CECAD) |
| Last Name: | García-Sáez |
| First Name: | Ana J. |
| Address: | Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany |
| Email: | ana.garcia@uni-koeln.de |
| Phone: | +49 221 478 84261 |
| Contributors: | Shashank Dadsena, Rodrigo Cuevas Arenas, Gonçalo Vieira, Susanne Brodesser, Manuel N. Melo, Ana J. García-Sáez |
Summary of all studies in project PR001935
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003114 | Lipidomics analyses in model membranes, isolated mitochondria and cellular systems to study how the local lipid environment affects BAX and BAK function during apoptosis. | Homo sapiens | University of Cologne | MS | 2024-03-13 | 1 | 40 | Uploaded data (19.8M)* |
