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.
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