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 IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)
Release
Date
VersionSamplesDownload
(* : 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)*
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