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Fig. 2

ID

ZDB-FIG-201208-12

Publication

Gut et al., 2020 - SUCLA2 mutations cause global protein succinylation contributing to the pathomechanism of a hereditary mitochondrial disease

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Fig. 2

Proteomics analysis of protein lysine succinylation.

a Workflow for label-free proteomics quantitation of succinyl-lysine residues in whole-cell lysates of fibroblasts and myotubes from SCL patients and controls. Samples were trypsin-digested. Succinylated lysines were enriched by immune affinity and analyzed by mass spectrometry (n = 2 control, n = 3 SCL patient-derived fibroblasts; n = 2 control, n = 1 patient-derived myotubes; A technical replicate of patient-derived myotube samples was used). b Venn diagram of total number of succinylated lysine sites identified in fibroblasts and myotubes. c Venn diagram of total number of proteins carrying succinyl-lysine sites. d Boxplot of fold-changes of succinyl-lysine mean intensities in fibroblasts and myotubes from patients compared to controls. Orange points indicate lysine marks enriched significantly more in patient samples, compared to controls. The boxplot shows the median, the first to third quartile, the 1.5x interquartile ranges, and outliers. e Table of identified SuK sites in fibroblasts and myotubes showing total numbers of SuK sites, numbers of SuK sites significantly enriched in SCL patient samples, and the median values of log₂-transformed ratios of patient-derived samples, compared to that from control cells. f Distribution of frequencies of succinylated lysine PTMs per detected protein. More than half of the proteins contain only one succinylated lysine. Oher proteins carry more than one SuK mark with a maximum of 27 SuK PTMs. g GO biological process term enrichment analysis of hyper-succinylated proteins from the fibroblast samples. Statistical significance was determined using fisher exact test. h Barplot of the 20 proteins with the highest numbers of SuK marks identified in our analysis. Highly succinylated proteins are found in different cellular compartments, including mitochondria, the nucleus, the endoplasmic reticulum and the cytosol. Protein ratio indicates levels of proteins in SCL patient-derived cells vs control cells. i Barplot of the 20 most dynamically affected succinylation marks in the absence of SUCLA2 as detected in this analysis. Source data are provided as a Source Data file. SuK= succinyl-lysine; TCA = tricarboxylic acid; BCAA = branched chain amino acid.

Expression Data

Expression Detail

Antibody Labeling

Phenotype Data

Phenotype Detail

Acknowledgments

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