Characterization of proteins involved in turnover of glycosomes in Trypanosoma brucei

Sleeping sickness is an infectious disease affecting humans in sub-Saharan Africa. It is caused by the protist Trypanosoma brucei which is transmitted by blood-feeding tsetse flies. This parasite possesses many unique features, including the organisation of the major part of the glycolytic pathway in peroxisome-like organelles known as glycosomes. This compartmentalisation has been shown to be essential for the viability of the parasite. During its life cycle, T. brucei proceeds through several stages. In its mammalian host, the parasite presents itself as a bloodstream form that, for its ATP supply, is dependent on glucose from the host’s blood and in the tsetse fly’s midgut it occurs as the procyclic form. In this latter stage the parasite prefers the less available glucose, but can also feed, for its energy, on amino acids such as proline and glutamine. The enzyme composition of glycosomes from each of these two stages is associated to the parasite’s metabolic needs. Bloodstream trypanosomes have 90% of the glycosomal enzyme content dedicated to glycolysis, while in glycosomes from procyclic cells this number drops to 40-50%, and the parasites develop a more diversified metabolism. Experiments performed in our laboratory have shown an increase in colocalisation of markers for glycosomes and the lysosome during the steps by which trypanosomes differentiate from the bloodstream to the procyclic form. This indicates that autophagy plays a role in the metabolic adaptation of the parasites during differentiation. It has been shown in yeast cells that peroxisomes reach a certain stage where they are no longer able to import matrix proteins from the cytosol. These organelles then, can be considered unable to adapt their enzyme content to changes in carbon source. We propose that a similar situation may happen in T. brucei where mature glycosomes that are rich in glycolytic enzymes and no longer able to import matrix proteins will be specifically degraded when the parasite differentiates into the procyclic form ...