Fatty acid elongases 1-3 have distinct roles in mitochondrial function, growth and lipid homeostasis inTrypanosoma cruzi

Abstract

AbstractTrypanosomatids are a diverse group of uniflagellate protozoa that include globally important pathogens such asTrypanosoma cruzi, the causative agent of Chagas disease. Trypanosomes lack the fatty acid synthase (FAS)-I system typically used forde novosynthesis of long chain fatty acids (LCFA) in other eukaryotes. Instead, these microbes have evolved a modular fatty acid elongase (ELO) system comprised of individual ELO enzymes that operate processively. The role of the ELO system in maintaining lipid homeostasis in trypanosomes has not been determined. Here we demonstrate that ELO2 and ELO3 are required for global lipidome maintenance in the insect stage ofT. cruziwhereas ELO1 is dispensable for this function. Instead, ELO1 activity is needed to sustain mitochondrial activity and normal growth. The cross-talk between microsomal ELO1 and the mitochondrion is a novel finding that merits examination of the trypanosomatid ELO pathway as critical for central metabolism.