CELE_K10C2.4, phi-43, K10C2.4

fah-1 encodes a putative fumarylacetoacetate hydrolase, orthologous to human FAH (OMIM:276700, mutated in type I tyrosinemia), that is required for tyrosine metabolism, resistance to oxidative and protein-folding stresses, and more generally for normally rapid growth, normal locomotion, fertility, and viability; fah-1 is expressed in hypodermis and intestine; the intestines of fah-1(RNAi) animals atrophy rapidly, and show an abnormally active oxidative stress response (seen via gst-4::GFP) and ER stress response (seen via hsp-4::GFP); while RNAi against enzymes upstream of fah-1 suppresses the fah-1(RNAi) phenotype, excess dietary tyrosine or homogentisic acid enhances it, and exogenous succinylacetone (SA) mimics it, consistent with the hypothesis that blocked SA metabolism is toxic in fah-1(RNAi) animals.

45848

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