Summary of project PR000991
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
| 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 |
Summary of all studies in project PR000991
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST001441 | Metabolomics of patient-derived fibroblasts | Homo sapiens | North Carolina State University | MS | 2020-08-06 | 1 | 56 | Uploaded data (4.4G)* |
