Studying peroxisome division at the molecular level

Introduction.

Peroxisomes can multiply by the division of existing ones and an important player in the division process is the peroxisomal membrane protein Pex11p. For many years the role of Pex11p in peroxisomal division was unclear. Recently, we have demonstrated that Pex11p acts as a master regulator of peroxisomal division, by not only initiating the division process by remodelling the peroxisomal membrane to form a new peroxisome, but also by regulating the activity of enzymes involved in the final step of peroxisome division. Therefore, further studies are vital to understand how Pex11p is able to combine these functions.

Description of the project.

Using the yeast Hansenula polymorpha as model organism, this project combines biochemical approaches with molecular dynamics simulations to elucidate the molecular mechanisms of Pex11p function in remodelling the peroxisomal membrane. In addition, advanced fluorescence microscopy will be employed to investigate the interplay between Pex11p and other members of the division machinery.

Relevant publications from the group

1.       Thomas AS, Krikken AM, van der Klei IJ, & Williams C (2015) Phosphorylation of Pex11p does not regulate peroxisomal fission in the yeast Hansenula polymorpha. Sci Rep.

2.       Williams C, et al. (2015) The membrane remodeling protein Pex11p activates the GTPase Dnm1p during peroxisomal fission. PNAS 112(20):6377-6382.

3.       Williams C & van der Klei I (2014) The Functions of Pex11 Family Proteins in Peroxisome Biology. Molecular Machines Involved in Peroxisome Biogenesis and Maintenance (Springer Vienna), pp 425-437.

4.       Opalinski L, Kiel J, Williams C, Veenhuis M, & van der Klei IJ (2011) Membrane curvature during peroxisome fission requires Pex11. EMBO J 30: 5-16.