Proteome adaptations in Ethe1-deficient mice indicate a role in lipid catabolism and cytoskeleton organization via post-translational protein modifications

authored by
Tatjana M. Hildebrandt, Ivano Di Meo, Massimo Zeviani, Carlo Viscomi, Hans Peter Braun
Abstract

Hydrogen sulfide is a physiologically relevant signalling molecule. However, circulating levels of this highly biologically active substance have to be maintained within tightly controlled limits in order to avoid toxic side effects. In patients suffering from EE (ethylmalonic encephalopathy), a block in sulfide oxidation at the level of the SDO (sulfur dioxygenase) ETHE1 leads to severe dysfunctions in microcirculation and cellular energy metabolism. We used an Ethe1-deficient mouse model to investigate the effect of increased sulfide and persulfide concentrations on liver, kidney, muscle and brain proteomes. Major disturbances in post-translational protein modifications indicate that the mitochondrial sulfide oxidation pathway could have a crucial function during sulfide signalling most probably via the regulation of cysteine S-modifications. Our results confirm the involvement of sulfide in redox regulation and cytoskeleton dynamics. In addition, they suggest that sulfide signalling specifically regulates mitochondrial catabolism of FAs (fatty acids) and BCAAs (branched-chain amino acids). These findings are particularly relevant in the context of EE since they may explain major symptoms of the disease.

Organisation(s)
Institute of Plant Genetics
External Organisation(s)
Istituto Nazionale Neurologico C Besta, Milan
Medical Research Council
Type
Article
Journal
Bioscience reports
Volume
33
Pages
575-584
No. of pages
10
ISSN
0144-8463
Publication date
25.07.2013
Publication status
Published
Peer reviewed
Yes
ASJC Scopus subject areas
Biophysics, Biochemistry, Molecular Biology, Cell Biology
Electronic version(s)
https://doi.org/10.1042/BSR20130051 (Access: Open)