Summary of project PR000991

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, 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.


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

Summary of all studies in project PR000991

Study IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)
(* : 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)*