Summary of Study ST001441
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 PR000991. The data can be accessed directly via it's Project DOI: 10.21228/M8M116 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 | ST001441 |
| Study Title | Metabolomics of patient-derived fibroblasts |
| Study Summary | 7 control fibroblasts samples and 7 patient-derived fibroblasts samples were collected at day 0 and day 5. Intracellular metabolites were extracted from cells cultured in 6 well plate while acyl-CoA and 5-methyltetrahydrofolate were extracted from cells cultured in 60 mm dish. |
| Institute | North Carolina State University |
| Last Name | Liu |
| First Name | Xiaojing |
| Address | Polk Hall, RM 128 |
| xliu68@ncsu.edu | |
| Phone | 9195154387 |
| Submit Date | 2020-06-11 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2020-08-06 |
| Release Version | 1 |
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Project:
| Project ID: | PR000991 |
| Project DOI: | doi: 10.21228/M8M116 |
| Project Title: | SUCLA2 mutations cause global protein succinylation contributing to the pathomechanism of a hereditary mitochondrial disease |
| Project Summary: | Mitochondrial acyl-coenzyme A species are emerging as important sources of protein modification and damage. Succinyl-CoA ligase (SCL) deficiency causes a mitochondrial encephalomyopathy of unknown pathomechanism. Here, we show that succinyl-CoA accumulates in cells derived from patients carrying recessive mutations in the tricarboxylic acid cycle (TCA) gene succinyl-CoA ligase subunit beta (SUCLA2) causing global protein hyper-succinylation. Using mass spectrometry, we quantified nearly 1000 protein succinylation sites on 366 proteins from patient-derived fibroblasts and myotubes. Interestingly, hyper-succinylated proteins are distributed across cellular compartments, and many are known targets of the (NAD+)-dependent desuccinylase SIRT5. To test the contribution of hyper-succinylation to disease progression, we developed a zebrafish model of the SCL deficiency, and find that SIRT5 gain-of-function reduces global protein succinylation and improves survival. Thus, increased succinyl-CoA levels contribute to the pathology of SCL deficiency through post-translational modifications. |
| Institute: | North Carolina State University |
| Last Name: | Liu |
| First Name: | Xiaojing |
| Address: | Polk Hall, RM 128 |
| Email: | xliu68@ncsu.edu |
| Phone: | 9195154387 |
