In or out? On the tightness of glycosomal compartmentalization of metabolites and enzymes in Trypanosoma brucei

• Glycosomes of trypanosomatids sequester glycolytic enzymes and metabolites.
• Pores in the glycosomal membrane allow diffusion of small metabolites.
• In intact glycosomes, metabolite diffusion through the pores is somehow restricted.
• Compartmentalization of ATP is essential for glycolytic function in trypanosomes.
• Cytosolic activity of glycosomal enzymes is often detrimental to trypanosomes.

Trypanosomatids sequester large parts of glucose metabolism inside specialised peroxisomes, called glycosomes. Many studies have shown that correct glycosomal compartmentalization of glycolytic enzymes is essential for bloodstream-form Trypanosoma brucei. The recent finding of pore-forming activities in glycosomal membrane preparations and extensions of the trypanosome glycolysis computer model with size-selective pores sparked again an old debate on the extent of (im)permeability of the glycosomal membrane and whether glycosomally located glycolytic enzymes could and should also be present with some activity in the cytosol. This review presents a critical discussion of the experimental and theoretical evidence for and against the different hypotheses.

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