Summary of project PR002482
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 PR002482. The data can be accessed directly via it's Project DOI: 10.21228/M8TC38 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002482 |
| Project DOI: | doi: 10.21228/M8TC38 |
| Project Title: | Complex II assembly drives metabolic adaptation to OXPHOS dysfunction. |
| Project Summary: | During acute oxidative phosphorylation (OXPHOS) dysfunction, the reverse activity of succinate dehydrogenase (Complex II) maintains the redox state of Coenzyme Q by utilizing either fumarate or oxygen as terminal electron acceptors. The tendency for one over another has been suggested to be tissue-specific, but the underlying mechanism and consequence of this is unknown. Using quantitative proteomics to screen a panel of HEK293T knockout cell lines, we identified an increase in SDHAF2 protein, a Complex II assembly factor that enhances the flavination of catalytic subunit SDHA, as critical for metabolic adaptation during OXPHOS stress in HEK293T cells. Loss of SDHAF2 during Complex III inhibition resulted in a reduction in Complex II F-site derived reactive oxygen species (ROS), a severe growth impairment, and a net reductive TCA cycle driven by an inability of mitochondria to support additional Complex II assembly. This in turn leads to use of fumarate as terminal electron acceptor at the cost of a ROS-mediated switch to glycolysis. Cell lines adapted to glycolysis did not accumulate SDHAF2 upon OXPHOS stress and exhibited a net reductive TCA cycle and mild growth phenotypes with or without SDHAF2 being present. Thus, our study reveals how Complex II assembly controls a balance between protection of the Q-pool and ROS-meditated signaling during oxidative stress in cells reliant on mitochondrial OXPHOS. |
| Institute: | University of Melbourne |
| Last Name: | Roopasingam |
| First Name: | Kugapreethan |
| Address: | 30 Flemington Rd, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC, Australia. |
| Email: | k.roopasingam@unimelb.edu.au |
| Phone: | 0434297212 |
Summary of all studies in project PR002482
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003959 | Steady state levels of polar metabolites HEK293T, SDHBKO and UQCRC1KO compared to WT cells. | Homo sapiens | University of Melbourne | MS | 2025-06-11 | 1 | 18 | Uploaded data (51.1M)* |
| ST003960 | Relative quantification of lactic acid secreted in media from cell lines treated with or without Antimycin A. | Homo sapiens | University of Melbourne | MS | 2025-06-11 | 1 | 12 | Uploaded data (38.5M)* |
| ST003961 | Measuring carbon flux into TCA cycle using 13C5-glutamine tracer metabolomics | Homo sapiens | University of Melbourne | MS | 2025-06-11 | 1 | 18 | Uploaded data (516.5M)* |
| ST003962 | Measuring TCA cycle directional fluxes using 13C5-glutamine | Homo sapiens | University of Melbourne | MS | 2025-06-11 | 1 | 42 | Uploaded data (41.6M)* |
| ST003968 | Measuring TCA cycle directional fluxes using 13C6-glucose | Homo sapiens | University of Melbourne | MS | 2025-06-12 | 1 | 27 | Uploaded data (1.9G)* |
