Peroxisomal membrane protein targeting

Our bodies contain many organs that each fulfil their own specialised functions. Similarly, the cells that make up these organs contain various organelles: membrane-bound structures that carry out specialised functions within the cell, such as peroxisomes, mitochondria and the nucleus.

Peroxisomes are multifunctional organelles that are crucial for human health and play a role in amongst others the breakdown and formation of specific lipids. One important aspect of peroxisome biology that is still poorly understood is how peroxisomes are formed and, more specifically, how peroxisomal membrane proteins, after being synthesised in the cytosol, arrive at their destination. The aim of this thesis was to better understand how proteins target to the peroxisomal membrane.

We uncovered the targeting signal of peroxisomal membrane protein Pxa1 in baker’s yeast. We also found that its interaction partner, Pxa2, ensures that some Pxa1 still arrives at the peroxisome in the absence of this targeting signal.

Many peroxisomal membrane proteins end up on mitochondria in the absence of peroxisomes. We discovered that in human cells that do contain peroxisomes, overexpression of peroxisomal membrane protein Pex14 resulted in its mislocalisation to mitochondria. This suggests that the absence of peroxisomes is not a requirement for mislocalisation of peroxisomal proteins to mitochondria, which was previously unknown.