Details
| Original language | English |
|---|---|
| Pages (from-to) | 575-584 |
| Number of pages | 10 |
| Journal | Bioscience reports |
| Volume | 33 |
| Issue number | 4 |
| Publication status | Published - 25 Jul 2013 |
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.
Keywords
- Branched-chain amino acid oxidation, Ethylmalonic encephalopathy, Hydrogen sulfide, Mitochondria, Redox regulation, Sulfur dioxygenase
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Biophysics
- Biochemistry, Genetics and Molecular Biology(all)
- Biochemistry
- Biochemistry, Genetics and Molecular Biology(all)
- Molecular Biology
- Biochemistry, Genetics and Molecular Biology(all)
- Cell Biology
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In: Bioscience reports, Vol. 33, No. 4, 25.07.2013, p. 575-584.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Proteome adaptations in Ethe1-deficient mice indicate a role in lipid catabolism and cytoskeleton organization via post-translational protein modifications
AU - Hildebrandt, Tatjana M.
AU - Di Meo, Ivano
AU - Zeviani, Massimo
AU - Viscomi, Carlo
AU - Braun, Hans Peter
PY - 2013/7/25
Y1 - 2013/7/25
N2 - 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.
AB - 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.
KW - Branched-chain amino acid oxidation
KW - Ethylmalonic encephalopathy
KW - Hydrogen sulfide
KW - Mitochondria
KW - Redox regulation
KW - Sulfur dioxygenase
UR - http://www.scopus.com/inward/record.url?scp=84881530220&partnerID=8YFLogxK
U2 - 10.1042/BSR20130051
DO - 10.1042/BSR20130051
M3 - Article
C2 - 23800285
AN - SCOPUS:84881530220
VL - 33
SP - 575
EP - 584
JO - Bioscience reports
JF - Bioscience reports
SN - 0144-8463
IS - 4
ER -