The conserved CXXC motif of hepatic stimulator substance is essential for its role in mitochondrial protection in H2O2-induced cell apoptosis.

Hepatic stimulator substance (HSS) protects liver cells from various toxins by alleviating lesions caused in the mitochondria. This paper demonstrates the necessity of the conserved CXXC catalytic motif (C62-C65) for the mitochondria-targeted anti-apoptotic activity of HSS. Mutating the conserved CXXC motif eliminated the protective effects against H(2)O(2)-induced apoptosis and diminished the protection of the mitochondria. However, the mutation of the other disulfide bond C91-C108 mainly preserved the protection of mitochondria by HSS, implying that the conserved CXXC motif and sulfhydryl oxidase (SOX) activity are essential for mitochondrial protection.