Summary of project PR001340
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 PR001340. The data can be accessed directly via it's Project DOI: 10.21228/M8HD8Q This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001340 |
| Project DOI: | doi: 10.21228/M8HD8Q |
| Project Title: | A ferroptosis defense mechanism mediated by glycerol 3-phosphate dehydrogenase 2 in mitochondria |
| Project Summary: | Mechanisms of defense against ferroptosis (an iron-dependent form of cell death induced by lipid peroxidation) in cellular organelles remain poorly understood, hindering our ability to target ferroptosis in disease treatment. In this study, metabolomic analyses revealed that treatment of cancer cells with glutathione peroxidase 4 (GPX4) inhibitors results in intracellular glycerol 3-phosphate (G3P) depletion. We further showed that supplementation of cancer cells with G3P attenuates ferroptosis induced by GPX4 inhibitors in a G3P dehydrogenase 2 (GPD2)-dependent manner; GPD2 deletion sensitizes cancer cells to GPX4 inhibition-induced mitochondrial lipid peroxidation and ferroptosis, and combined deletion of GPX4 and GPD2 synergistically suppresses tumor growth by inducing ferroptosis in vivo. Mechanistically, inner mitochondrial membrane-localized GPD2 couples G3P oxidation with ubiquinone reduction to ubiquinol, which acts as a radical-trapping antioxidant to suppress ferroptosis in mitochondria. Taken together, these results reveal that GPD2 participates in ferroptosis defense in mitochondria by generating ubiquinol. |
| Institute: | University of Texas MD Anderson Cancer Center |
| Last Name: | Gan |
| First Name: | Boyi |
| Address: | 6565 MD Anderson Blvd, Houston, TX 77030 |
| Email: | bgan@mdanderson.org |
| Phone: | 713-792-8653 |
Summary of all studies in project PR001340
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002115 | LC-MS analysis of metabolic changes induced by GPX4 inhibitor treatment in cultured HT1080 cells | Homo sapiens | University of Texas MD Anderson Cancer Center | MS | 2022-04-14 | 1 | 12 | Uploaded data (265.8M)* |
