Developmental regulation of mitochondrial biogenesis inTrypanosoma brucei

Abstract

The metabolism of Trypanosoma brucei undergoes a significant change as the parasite differentiates from the mammalian bloodstream form to the form found in the tse-tse fly vector. Because the mitochondria of bloodstream form cells lack cytochromes and several key citric acid cycle enzymes, the metabolism of these cells is mostly limited to glycolysis. The reducing equivalents generated by this process are passed to oxygen by a plant-like alternative oxidase. As cells differentiate to the insect form, they begin to oxidatively metabolize proline. The mitochondria of insect form cells contain functional, cytochrome-mediated electron transport chains and have complete complements of citric acid cycle enzymes. Although the characterization is far from complete, the nuclear and mitochondrial genes involved in the expression of these mitochondrial functions appear to be developmentally regulated at posttranscriptional and posttranslational levels. This review outlines some of the molecular processes that are associated with the developmental regulation of mitochondrial biogenesis and suggests some possible mechanisms of regulation.

The Single Dynamin-like Protein of Trypanosoma brucei Regulates Mitochondrial Division and Is Not Required for Endocytosis

“…3A), and any overlap is probably a result of the extensive distribution of the mitochondrion. Similar staining patterns were observed for the tested markers in bloodstream form cells, but less mitochondrial signal was observed due to reduced mitochondrial function in this life stage (data not shown) (7).…”

“…The T. brucei life cycle alternates between the mammalian host stages and insect vector stages, which are coupled to extensive alterations in morphology and metabolism (5,6). In particular, the mitochondrion undergoes extensive remodeling at the structural and biochemical level (7). Procyclic trypanosomes (PCF) 1 maintain a developed mitochondrion with abundant cristae, whereas in the replicative slender bloodstream form (BSF), the mitochondrion is greatly reduced with scarcely any cristae.…”

“…The bloodstream form lacks cytochromes, several key enzymes of the Krebs cycle, and is incapable of full oxidative phosphorylation (8). This remodeling reflects fundamental differences in the energy metabolism between the two life cycle stages (7,9).…”

Mitochondrial Development during Life Cycle Differentiation of African Trypanosomes: Evidence for a Kinetoplast-dependent Differentiation Control Point

“…The developmental regulation of mitochondrial activity is a central component of the trypanosome life cycle (Priest and Hajduk, 1994). This reflects their metabolic requirements in the bloodstream or in the tsetse.…”

A Developmentally Regulated Aconitase Related to Iron-regulatory Protein-1 Is Localized in the Cytoplasm and in the Mitochondrion of Trypanosoma brucei

“…Hence, slender forms lack significant amounts of Krebs cycle enzymes (5), and their residual mitochondrion does not contribute to ATP production. At the peak of a parasitemic wave, slender forms differentiate into a quiescent, cell cycle-arrested stage with stumpy morphology (stumpy form) which has a more developed mitochondrion and expresses citric acid cycle activities and an incomplete electron transport chain (5)(6)(7)(8). In culture, differentiation to the stumpy stage is induced by a cell density sensing mechanism acting via the cAMP second messenger pathway (9,10).…”