Major pathways of compartmentalized energy metabolism in bloodstream (a) and procyclic (b) life cycle stages of the flagellated and fully oxygen-dependent protist parasite Trypanosoma brucei. Major pathways of compartmentalized energy metabolism in bloodstream (a) and procyclic (b) life cycle stages of the flagellated and fully oxygen-dependent protist parasite Trypanosoma brucei. The maps are redrawn based on data reported previously (54, 500a, 538). (a) In bloodstream forms, Trypanosoma brucei mitochondria help to maintain cell redox homeostasis via glycerol-3-phosphate dehydrogenase and alternative oxidase, which, together with ubiquinone, constitute the whole O2-consuming respiratory chain, which does not, however, produce ATP. The inner mitochondrial membrane ATPase works in reverse; that is, it pumps protons to the intermembrane space while hydrolyzing ATP to ADP. The major metabolic end product pyruvate is generated in the cytosol. The photograph shows a long slender bloodstream form of Trypanosoma brucei with a length of ca. 25 μm (circles in the background are erythrocytes). (Photograph by Rob Koelewijn, Harbor Hospital, Rotterdam, Netherlands.) (b) Energy metabolism is more complex in procyclic T. brucei stages. Succinate is generated both in glycosomes by a soluble fumarate reductase and in mitochondria via a recently functionally characterized soluble mitochondrial fumarate reductase (90). Acetate is produced in mitochondria mainly by means of the acetate:succinate CoA-transferase/succinyl-CoA synthetase cycle, but an alternative pathway is also present (413). In T. brucei, no lactate is formed from pyruvate (538); instead, another end product commonly found in facultative anaerobic animals, alanine, is produced by alanine aminotransferase. The respiratory chain contains not only an alternative oxidase and glycerol-3-phosphate dehydrogenase but also an alternative rotenone-insensitive NADH dehydrogenase (90). Abbreviations: CI to CIV, respiratory complexes I to IV; UQ, ubiquinone; C, cytochrome c; A, ATPase; AOX, alternative oxidase; AN, alternative, rotenone-insensitive NADH dehydrogenase; GPDH, glycerol-3-phosphate dehydrogenase; G3P, glycerol-3-phosphate; DHAP, dihydroxyacetone phosphate; GAP, glyceraldehyde-3-phosphate; PGA, 3-phosphoglycerate; [2A], acetate:succinate CoA-transferase (subfamily 1A); [3], succinyl-CoA synthetase; [5], malic enzyme; [6], pyruvate dehydrogenase complex; [8], fumarase; [9], pyruvate kinase; [10], phosphoenolpyruvate carboxykinase (ATP dependent); [11], malate dehydrogenase; [18], alanine aminotransferase; [24], fumarate reductase (soluble, NADH dependent); [42], α-ketoglutarate dehydrogenase; [43], citrate synthase. Miklós Müller et al. Microbiol. Mol. Biol. Rev. 2012; doi:10.1128/MMBR.05024-11