Role of Heme and Heme-Proteins in Trypanosomatid Essential Metabolic Pathways

Figure 3

Schematic representation of transport, trafficking, and uses of heme in a trypanosomatid epimastigote. The amplified areas correspond to the mitochondrial and endoplasmic reticulum regions (above and below resp.) where the heme-proteins mentioned in the text are located. In the mitochondrion, heme B is internalized by one or several unknown transport systems. Once in the matrix (or alternatively in the intermembrane space) heme B is transformed into heme O by the membrane-bound heme O synthase (Cox10) enzyme, and immediately later heme O is converted into heme A by the heme A synthase (Cox15) enzyme [17]. Finally heme A is incorporated into the cytochrome c oxidase complex by an unknown mechanism. In the endoplasmic reticulum cytochrome b5 takes electrons from several donors, such as NADH, FADH, and other reduced compounds (not shown), and serves in turn as an electron donor for the various transmembrane fatty acid desaturases and other ER proteins such as CYP51. Alternatively, front-end desaturases contain a cytochrome-type domain which serves as their own electron donor. See text for more details. Abbreviations: H: heme B; HA: heme A; HO: heme O; C: c-type cytochrome; Q: quinone; II, III, IV: complexes II, III, and IV of the electron transport chain, respectively.