Persulfide dioxygenase ETHE1, mitochondrial

ETHE1 is a mitochondrial persulfide dioxygenase that catalyzes the oxidation of cysteine persulfide residues derived from hydrogen sulfide metabolism, playing a critical role in preventing toxic H₂S accumulation in mitochondria by consuming molecular oxygen and transferring persulfides to acceptors such as glutathione (UniProt: O95571). The protein has also been reported to suppress p53-induced apoptosis by sequestering RELA/NFKB3 in the cytoplasm. ETHE1 is associated with ethylmalonic encephalopathy, a severe autosomal recessive neurodevelopmental disorder characterized by developmental delay, regression, and metabolic acidosis (UniProt: O95571).

In Alzheimer's disease, ETHE1 is significantly upregulated in post-mortem AD brain tissue compared to age-matched controls (mean log₂FC = 0.24, Chaparral AD proteomics), detected across subcellular fractions in TMT-labeled mass spectrometry analysis. This upregulation may suggest altered mitochondrial hydrogen sulfide metabolism and increased oxidative stress responses in AD pathology, though the functional consequences remain to be established.