Rewiring and regulation of cross-compartmentalized metabolism in protists

Abstract

Plastid acquisition, endosymbiotic associations, lateral gene transfer, organelle degeneracy or even organelle loss influence metabolic capabilities in many different protists. Thus, metabolic diversity is sculpted through the gain of new metabolic functions and moderation or loss of pathways that are often essential in the majority of eukaryotes. What is perhaps less apparent to the casual observer is that the sub-compartmentalization of ubiquitous pathways has been repeatedly remodelled during eukaryotic evolution, and the textbook pictures of intermediary metabolism established for animals, yeast and plants are not conserved in many protists. Moreover, metabolic remodelling can strongly influence the regulatory mechanisms that control carbon flux through the major metabolic pathways. Here, we provide an overview of how core metabolism has been reorganized in various unicellular eukaryotes, focusing in particular on one near universal catabolic pathway (glycolysis) and one ancient anabolic pathway (isoprenoid biosynthesis). For the example of isoprenoid biosynthesis, the compartmentalization of this process in protists often appears to have been influenced by plastid acquisition and loss, whereas for glycolysis several unexpected modes of compartmentalization have emerged. Significantly, the example of trypanosomatid glycolysis illustrates nicely how mathematical modelling and systems biology can be used to uncover or understand novel modes of pathway regulation.

Biochemistry and Evolution of Anaerobic Energy Metabolism in Eukaryotes

“…Such minor mistargeting is all the more likely for highly expressed proteins, such as those involved in core energy metabolism, and if a small amount of a whole pathway is present, it could readily become a unit of function and, hence, a unit upon which natural selection could act to generate more or less of that specific compartmentation variant. Clearly, pathways and enzymes are often recompartmentalized during evolution, and the minor mistargeting mechanism (307) could, in principle, explain how whole pathways can attain new states of subcellular localization (160).…”

Spatial Distribution of Cellular Function: The Partitioning of Proteins between Mitochondria and the Nucleus in MCF7 Breast Cancer Cells

“…38,70,87 In doing so we might remember that cells seem to have a high degree of plasticity and that, for example, in protists there can be major differences in the organization of subcellular location/function. 106 We might also take note of complex systems theory and begin to consider whether the functional diversity, partial overlap with other processes, highly diverse networks and spatial distribution characteristics may be a reflection of the need for robustness in complex systems. 107 Summary of experimental MS data and GO CC annotation terms for proteins in oxidative phosphorylation complexes 1-5. nd denotes proteins that were not detected.…”

Spatial Reorganization of Saccharomyces cerevisiae Enolase To Alter Carbon Metabolism under Hypoxia

“…Some glycolytic enzymes, such as GAPDH (glyceraldehyde-3-phosphate dehydrogenase), aldolase, and lactate dehydrogenase, have been found to be associated with the cytoskeleton (29,30), erythrocyte membrane (31), muscle (32), or each other (33)(34)(35). The association of glycolytic enzymes has been considered to contribute to metabolic efficiency by increasing pyruvate production (25,26); however, this notion is still under debate (36,37). To date, the regulation of metabolic pathways via the association of metabolic enzymes has been found only in plants, in which 10 glycolytic enzymes were identified to be associated with mitochondria for supporting respiration (38,39).…”