Deficiency of mitochondrial
sulfur dioxygenase (ETHE1) causes the severe metabolic disorder
ethylmalonic encephalopathy, which is characterized by early-onset
encephalopathy and defective
cytochrome C oxidase because of
hydrogen sulfide accumulation. Although the severe systemic consequences of the disorder are becoming clear, the molecular effects are not well defined. Therefore, for further elucidating the effects of ETHE1-deficiency, we performed a large scale quantitative proteomics study on liver tissue from ETHE1-deficient mice. Our results demonstrated a clear link between ETHE1-deficiency and redox active
proteins, as reflected by downregulation of several
proteins related to oxidation-reduction, such as different
dehydrogenases and
cytochrome P450 (CYP450) members. Furthermore, the
protein data indicated impact of the ETHE1-deficiency on metabolic reprogramming through upregulation of glycolytic
enzymes and by altering several heterogeneous
ribonucleoproteins, indicating novel link between ETHE1 and gene expression regulation. We also found increase in total
protein acetylation level, pointing out the link between ETHE1 and acetylation, which is likely controlled by both redox state and cellular metabolites. These findings are relevant for understanding the complexity of the disease and may shed light on important functions influenced by ETHE1 deficiency and by the concomitant increase in the
gaseous mediator hydrogen sulfide. All MS data have been deposited in the ProteomeXchange with the dataset identifiers PXD002741 (http://proteomecentral.proteomexchange.org/dataset/PXD002741) and PXD002742 (http://proteomecentral.proteomexchange.org/dataset/PXD002741).