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C.W.T. van Roermund PhD

Position
Research Associate
Main activities
Education, Research
Specialisation
Scientist: In vivo and in vitro transport of metabolites across the peroxisomal membrane
Focus of research

In recent years, much progress has been made with respect to the unravelling of the functions of peroxisomes in metabolism, and it is now well established that peroxisomes are indispensable organelles, especially in higher eukaryotes. Peroxisomes catalyse a number of essential metabolic functions including fatty acid beta-oxidation, ether phospholipid biosynthesis, fatty acid a-oxidation and glyoxylate detoxification. The involvement of peroxisomes in these metabolic pathways necessitates the transport of metabolites in and out of peroxisomes. Recently, considerable progress has been made in the characterization of metabolite transport across the peroxisomal membrane. Peroxisomes posses several specialized transport systems to transport metabolites. This is exemplified by the identification of a specific transporter for adenine nucleotides and several half-ABC (ATP-binding cassette) transporters (ABCD1-3) which may be present as hetero- and homo-dimers. The importance to investigate permeability properties of the peroxisomal membrane is underlined by the existence of a number of different genetic diseases. One of these peroxisomal disorders is X-linked adrenoleukodystrophy (X-ALD). The gene mutated in X-linked adrenoleukodystrophy (X-ALD) codes for the HsABCD1 protein, a member of the superfamily of ATP-binding cassette (ABC) transporters and required for fatty acid transport across the peroxisomal membrane. Although defective HsABCD1 results in the accumulation of very long-chain fatty acids in plasma of X-ALD patients, there is still no direct biochemical evidence that HsABCD1 actually transports very long-chain fatty acids.

To study the transport of fatty acids across the peroxisomal membrane and their metabolism in vivo we have chosen Saccharomyces cerevisiae as a model system. An important advantage of studies in the yeast S. cerevisiae is that peroxisomes are the only organelles in which beta-oxidation of fatty acids takes place, in contrast to the situation in mammalian cells. In the latter case peroxisomes as well as mitochondria participate in fatty acid oxidation. Secondly, we study the mechanism of metabolic transport in vitro by  functional reconstitution of peroxisomal transporters into proteoliposomes. The resolution of the mechanism of these transporters is utmost significance for our thinking about peroxisomal disorders e.g. X-linked adrenoleukodystrophy and its pathophysiological mechanisms and future therapies.

Key publications
  • Strijbis Karin, van Roermund Carlo W., van den Burg Janny, van den Berg Marlene, Hardy Guy P. M., Wanders Ronald J., Distel Ben Contributions of Carnitine Acetyltransferases to Intracellular Acetyl Unit Transport in Candida albicans Journal of biological chemistry 2010;285 (32):24335-24346 [PubMed]
  • Ofman Rob, Dijkstra Inge M. E., van Roermund Carlo W. T., Burger Nena, Turkenburg Marjolein, van Cruchten Arno, van Engen Catherine E., Wanders Ronald J. A., Kemp Stephan The role of ELOVL1 in very long-chain fatty acid homeostasis and X-linked adrenoleukodystrophy EMBO molecular medicine 2010;2 (3):90-97 [PubMed]
  • van Roermund Carlo W. T., Visser Wouter F., Ijlst Lodewijk, van Cruchten Arno, Boek Maxim, Kulik Wim, Waterham Hans R., Wanders Ronald J. A. The human peroxisomal ABC half transporter ALDP functions as a homodimer and accepts acyl-CoA esters FASEB journal 2008;22 (12):4201-4208 [PubMed]
  • van Roermund Carlo W. T., de Jong Mark, Ijlst Lodewijk, van Marle Jan, Dansen Tobias B., Wanders Ronald J. A., Waterham Hans R. The peroxisomal lumen in Saccharomyces cerevisiae is alkaline Journal of cell science 2004;117 (Part 18):4231-4237 [PubMed]
  • van Roermund C. W. T., Waterham H. R., IJlst L., Wanders R. J. A. Fatty acid metabolism in Saccharomyces cerevisiae Cellular and molecular life sciences 2003;60 (9):1838-1851 [PubMed]
All Publications
Curriculum Vitae

Personal Details
Name: C.W.T. van Roermund
Address: Margaklompelaan 4
Postal code: 1945ZL
City: Beverwijk
Telefone: +31 20 566 3827
Fax: +31 20 696 2596
E-mail: c.vanroermund@amc.uva.nl
 

Education
University Utrecht; Biology; Main subject Molecular Biology. Title: Characterization of 3-oxoacyl-CoA thiolase.
Thesis: Fatty acid oxidation in Saccharomyces cerevisiae (2002) Biochemistry, Academic Medical Centre (AMC), Prof. Dr. H.F. Tabak en Prof. Dr. R.J.A. Wanders.

2002-2010: Scientist: Laboratory Genetic Metabolic Diseases (GMZ).
Academic Medical Centre (AMC), Prof. Dr. R.J.A. Wanders.

Work experience
1992 Prof dr. Mannearts, University in Leuven, België; Enzymology
1995 Prof dr. Hoefler, University in Graz, Oostenrijk; DNA and RNA
1999 Prof dr. Palmieri, University in Bari, Italië; Isolation membrane proteins.
2008 Prof dr. van Veen, University in Cambridge, Engeland; Functional reconstitution of transporters into proteoliposomes.

 

Research programmes

Prof. H.R. Waterham PhD (Functional Genetics of Metabolic Diseases)

Prof. R.J.A. Wanders PhD (Biochemistry & Enzymology of Metabolic Disorders)