COMPARTMENTATION OF PHOSPHOGLYCERATE KINASE IN TRYPANOSOMA-BRUCEI PLAYS A CRITICAL ROLE IN PARASITE ENERGY-METABOLISM

African trypanosomes compartmentalize glycolysis in a microbody, the g lycosome, When growing in the mammalian bloodstream, trypanosomes cont ain only a rudimentary mitochondrion, and the first seven glycolytic e nzymes, including phosphoglycerate kinase, are located in the glycosom e, Procyclic trypanosomes, growing in the gut of tsetse flies, possess a fully developed mitochondrion that is active in oxidative phosphory lation. The first six glycolytic enzymes are still glycosomal, but pho sphoglycerate kinase is now found in the cytosol, We demonstrate here that bloodstream trypanosomes are killed by expression of cytosolic ph osphoglycerate kinase, The toxicity depends on both enzyme activity an d cytosolic location, One possible explanation is that cytosolic phosp hoglycerate kinase creates an ATP-generating shunt in the cytosol, thu s preventing full ATP regeneration in the glycosome and ultimately inh ibiting the first, ATP-consuming, steps of glycolysis.