TST knockout liver proteome iTRAQ and persulfidome
Ontology highlight
ABSTRACT: Impaired hepatic glucose and lipid metabolism are hallmarks of type–2 diabetes. Increased sulfide production or sulfide–donor compounds may beneficially regulate hepatic metabolism. Disposal of sulfide through the sulfide oxidation pathway (SOP) is critical for maintaining sulfide within a safe physiological range. We show that mice lacking the liver–enriched mitochondrial SOP enzyme thiosulfate sulfur–transferase (Tst—/— mice) exhibit high circulating sulfide, increased gluconeogenesis, hypertriglyceridemia and fatty liver. Unexpectedly, hepatic sulfide levels are normal in Tst—/— mice due to exaggerated induction of sulfide disposal, with an associated suppression of global protein persulfidation and nuclear respiratory factor–2 target protein levels. Hepatic proteomic and persulfidomic profiles converge on gluconeogenesis and lipid metabolism, revealing a selective deficit in medium–chain fatty acid oxidation in Tst—/— mice. We reveal a critical role for TST in hepatic metabolism that has implications for sulfide-donor strategies in the context of metabolic disease.
INSTRUMENT(S): LTQ Orbitrap Elite
ORGANISM(S): Mus Musculus (mouse)
TISSUE(S): Liver
SUBMITTER: Pauline Ward
LAB HEAD: Nik Morton
PROVIDER: PXD028909 | Pride | 2021-11-11
REPOSITORIES: Pride
ACCESS DATA