Summary of Study ST003398
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 PR002104. The data can be accessed directly via it's Project DOI: 10.21228/M8NJ9Q This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST003398 |
| Study Title | Specific activation of the integrated stress response (ISR) uncovers regulation of lipid droplet biogenesis |
| Study Type | Biology |
| Study Summary | U2OS cells were treated with Dimerizer-PERK for 0h,1h,2h,4h,8h and 24h. Lipidomics analysis using LC-MS was performed on these samples to understand the regulation of cellular lipidome upon ISR activation |
| Institute | Calico Life Sciences |
| Department | Department of Mass Spectrometry-Technology Lab |
| Laboratory | Metabolomics Lab |
| Last Name | Vu |
| First Name | Ngoc |
| Address | 1130 Veterans BLVD, South San Francisco, CA 94080 |
| ngoc@calicolabs.com | |
| Phone | 650-420-5430 |
| Submit Date | 2024-08-08 |
| Num Groups | 6 |
| Total Subjects | 18 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-09-03 |
| Release Version | 1 |
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Project:
| Project ID: | PR002104 |
| Project DOI: | doi: 10.21228/M8NJ9Q |
| Project Title: | Specific activation of the integrated stress response uncovers regulation of central carbon metabolism and lipid droplet biogenesis |
| Project Type: | Biology |
| Project Summary: | The integrated stress response (ISR) enables cells to cope with a variety of insults, but its specific contribution to downstream cellular outputs remains unclear. Using a synthetic tool, we selectively activate the ISR without co-activation of parallel pathways and define the resulting cellular state with multi-omics profiling. We identify time- and dose-dependent gene expression modules, with ATF4 driving only a small but sensitive subgroup that includes amino acid metabolic enzymes. This ATF4 response affects cellular bioenergetics, rerouting carbon utilization towards amino acid production and away from the tricarboxylic acid cycle and fatty acid synthesis. We also find an ATF4-independent reorganization of the lipidome that promotes DGAT-dependent triglyceride synthesis and accumulation of lipid droplets. While DGAT1 is the main driver of lipid droplet biogenesis, DGAT2 plays an essential role in buffering stress and maintaining cell survival. Together, we demonstrate the sufficiency of the ISR in promoting a previously unappreciated metabolic state. |
| Institute: | Calico Life Sciences |
| Department: | Department of Mass Spectrometry-Technology Lab |
| Laboratory: | Metabolomics Lab |
| Last Name: | Vu |
| First Name: | Ngoc |
| Address: | 1130 Veterans BLVD, South San Francisco, CA 94080 |
| Email: | ngochmvu@gmail.com |
| Phone: | 6504205430 |
| Publications: | Labbe, Lebon & King et al., Specific activation of the integrated stress response uncovers regulation of central carbon metabolism and lipid droplet biogenesis.Nat Comm.2024 |
