Tsc13p is required for fatty acid elongation and localizes to a novel structure at the nuclear-vacuolar interface in Saccharomyces cerevisiae

The TSC13/YDL015c gene was identified in a screen for suppressors of the ca lcium sensitivity of csg2 Delta mutants that are defective in sphingolipid synthesis. The fatty acid moiety of sphingolipids in Saccharomyces cerevisi ae is a very long chain fatty acid (VLCFA) that is synthesized by a microso mal enzyme system that lengthens the palmitate produced by cytosolic fatty acid synthase by two carbon units in each cycle of elongation. The TSC13 ge ne encodes a protein required for elongation, possibly the enoyl reductase that catalyzes the last step in each cycle of elongation. The tsc13 mutant accumulates high levels of long-chain bases as well as ceramides that harbo r fatty acids with chain lengths shorter than 26 carbons. These phenotypes are exacerbated by the deletion of either the ELO2 or ELO3 gene, both of wh ich have previously been shown to be required for VLCFA synthesis. Compromi sing the synthesis of malonyl coenzyme A (malonyl-CoA) by inactivating acet yl-CoA carboxylase in a tsc13 mutant is lethal, further supporting a role o f Tsc13p in VLCFA synthesis. Tsc13p coimmunoprecipitates with Elo2p and Elo 3p, suggesting that the elongating proteins are organized in a complex. Tsc 13p localizes to the endoplasmic reticulum and is highly enriched in a nove l structure marking nuclear-vacuolar junctions.