Figure 8.

Working model for how SKN-1-regulated SPHK-1 signaling regulates neuropeptide secretion. A, During normal conditions, SKN-1 levels are kept low by WDR-23, expression of SKN-1 targets is low, and SPHK-1 abundance on the outer mitochondrial membrane is high. S1P generated by SPHK-1 in the intestine directly or indirectly promotes neuropeptide secretion from motor neurons. B, During high oxidative stress conditions, PMK-1 promotes SKN-1 nuclear translocation, SKN-1 target genes are expressed, and SPHK-1 mitochondrial abundance is low. Decreased generation of S1P by SPHK-1 leads to a reduction in neuropeptide secretion from motor neurons.