A piggybacking mechanism enables peroxisomal localization of the glyoxylate cycle enzyme Mdh2 in yeast.

Eukaryotic cells evolved organelles that allow the compartmentalization and regulation of metabolic processes. Knowledge on molecular mechanisms that allow temporal and spatial organization of enzymes within organelles is therefore critical for understanding eukaryotic metabolism. Here we show that the yeast malate dehydrogenase 2 (Mdh2) is dually localized to the cytosol and to peroxisomes and is targeted to peroxisomes via association with Mdh3 and a Pex5-dependent piggybacking mechanism. The dual localization of Mdh2 contributes to our understanding of the glyoxylate cycle and provides a new perspective on compartmentalization of cellular metabolism, which is critical for the perception of metabolic disorders and aging.