PEROXISOMAL BETA-OXIDATION OF POLYUNSATURATED FATTY-ACIDS IN SACCHAROMYCES-CEREVISIAE - ISOCITRATE DEHYDROGENASE PROVIDES NADPH FOR REDUCTION OF DOUBLE-BONDS AT EVEN POSITIONS

The beta-oxidation of saturated fatty acids in Saccharomyces cerevisia e is confined exclusively to the peroxisomal compartment of the cell, Processing of mono- and polyunsaturated fatty acids with the double bo nd at an even position requires, in addition to the basic beta-oxidati on machinery, the contribution of the NADPH-dependent enzyme 2,4-dieno yl-CoA reductase, Here we show by biochemical cell fractionation studi es that this enzyme is a typical constituent of peroxisomes. As a cons equence, the P-oxidation of mono-and polyunsaturated fatty acids with double bonds at even positions requires stoichiometric amounts of intr aperoxisomal NADPH. We suggest that NADP-dependent isocitrate dehydrog enase isoenzymes function in an NADP redox shuttle across the peroxiso mal membrane to keep intraperoxisomal NADP reduced, This is based on t he finding of a third NADP-dependent isocitrate dehydrogenase isoenzym e, Idp3p, next to the already known mitochondrial and cytosolic isoenz ymes, which turned out to be present in the peroxisomal matrix. Our pr oposal is strongly supported by the observation that peroxisomal Idp3p is essential for growth on the unsaturated fatty acids arachidonic, l inoleic and petroselinic acid, which require 2,4-dienoyl-CoA reductase activity, On the other hand, growth on oleate which does not require 2,4-dienoyl-CoA and NADPH is completely normal in Delta idp3 cells.