Flexible Cooperation Between Peroxisomes and the Endoplasmic Reticulum During Lipid Synthesis of Dictyostelium

Ether lipids in varying amounts are membrane constituents and storage material in the protist and animal kingdoms, but are largely absent from fungi and plants. Their biosynthesis pathway starts in the peroxisome and involves a set of well-conserved enzymes. Only one step, the reduction of alkyl-dihydroxyacetone-phosphate to alkyl-glycerol-3-phosphate, is mediated by so-called short-chain dehydrogenases/reductases, which are members of huge protein families. Here, using GFP fusions, we identify a peroxisomal enzyme in Dictyostelium, as well as a highly related protein residing in the endoplasmic reticulum. Single-gene knockouts indicate that these enzymes largely compensate for one another, suggesting a flexible redistribution of lipid metabolites between these organelles. The double knockout, however, is severely affected in ether lipid composition and displays a clear growth retardation. The defects can also be reverted by expression of the cognate yeast enzyme, demonstrating conservation of this metabolic step across kingdoms of life.