The University of Sheffield
Department of Molecular Biology and Biotechnology

Fungal Cell Biology


Dr E Hettema
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Eukaryotic cells contain many functionally distinct membrane-bounded compartments called organelles. During cell division, organelles must be accurately multiplied and partitioned to daughter cells. To understand how organelles are inherited, we need to unravel the molecular mechanisms of organelle multiplication and transport and how these processes are coordinated with the cell cycle.

 

My group uses bakers yeast (Saccharomyces cerevisiae) as a model organism to study membrane trafficking and membrane fission processes. We have discovered that one of the organelles, the peroxisome, multiplies by growth and division. The endoplasmic reticulum supplies peroxisomes with membrane constituents allowing these organelles to grow. Subsequent fission is mediated by the dynamin-related proteins Vps1 and Dnm1. Proper distribution of peroxisomes relies on two opposing processes, 1) actin/myosin-based transport to the bud and 2) retention in the mother.

 

Peroxisome segregation during the budding yeast cell cycle. Figure 1. Peroxisome segregation during the budding yeast cell cycle.

 

Current lines of research

My group is focussing on how peroxisome abundance is maintained and how this is integrated with other cellular processes. More specifically, we are studying the role of the ER in peroxisome formation, how peroxisomes are segregated during cell division, the contribution of autophagy on peroxisome turnover and the observed peroxisome proliferation in response to defects in mitochondrial respiration and oxidative phosphorylation. We use a variety of molecular cell biological approaches including live-cell imaging, yeast genetics, proteomics and protein-protein interaction studies. Our findings in yeast will be tested for evolutionary conservation in other model systems including mammalian tissue culture cells.

 

Selected Publications

A dual function for Pex3p in peroxisome formation and inheritance. Munck JM, Motley AM, Nuttall JM, Hettema EH. J Cell Biol. 2009 Nov 16;187(4):463-71.
How peroxisomes multiply. Hettema EH, Motley AM. J Cell Sci. 2009 Jul 15;122(Pt 14):2331-6.
Dnm1p-dependent peroxisome fission requires Caf4p, Mdv1p and Fis1p. Motley AM, Ward GP, Hettema EH. J Cell Sci. 2008 May 15;121(Pt 10):1633-40.
Yeast peroxisomes multiply by growth and division. Motley AM, Hettema EH. J Cell Biol. 2007 Jul 30;178(3):399-410.
Hoepfner D., van den Berg M., Philippsen P., Tabak HF., Hettema EH. A role for Vps1p, actin, and the Myo2 motor in peroxisome abundance and inheritance in Saccharomyces cerevisiae. J. Cell Biol. 155, 979-90 (2001)
van Roermund CWT., Tabak HF., van den Berg M., Wanders RJA., Hettema EH. Pex11p plays a primary role in medium-chain fatty acid oxidation, a process that affects peroxisome number and size in Saccharomyces cerevisiae. J. Cell Biol. 150, 489-98 (2000).
Hettema, EH., Girzalsky, W., van den Berg, M., Erdmann, R. and Distel, B. S. cerevisiae Pex3 and Pex19 are required for proper localisation and stability of peroxisomal membrane proteins. EMBO J. 19, 223-233 (2000)