Functions and biogenesis of peroxisomes in humans in relation to peroxisomal disorders

Seminar

Title: Functions and biogenesis of peroxisomes in humans in relation to peroxisomal disorders

Speaker: Prof. dr. Ronald J.A. Wanders

Affiliation: Lab Genetic Metabolic Diseases
                Academic Medical Center, University of Amsterdam

Host: Cláudio M. Gomes, Protein Biochemistry, Folding & Stability Laboratory

Abstract:

Peroxisomes are subcellular organelles just like mitochondria and lysosomes, which have long remained underrated as organelles with no particular role in human physiology. Over the years it became clear that this view is incorrect and that peroxisomes in fact catalyze a number of essential metabolic functions in higher eukaryotes, including humans. The main functions of peroxisomes include: (1.) fatty acid beta-oxidation; (2.) etherphospholipid (plasmalogen) biosynthesis; (3.) fatty acid alpha-oxidation, and (4.) glyoxylate detoxification. The best evidence that peroxisomes are indeed indispensable organelles in human beings comes from studies on a rapidly fatal autosomal recessive disease, called Zellweger syndrome, which is characterized by the total absence of peroxisomes as caused by mutations in one of the many genes, whose protein products are required for proper peroxisome formation.

As a consequence of the inability to synthesize peroxisomes all peroxisomal functions are lost in Zellweger patients which leads to a number of metabolic abnormalities, including the accumulation of a range of different metabolites whose degradation is dependent on peroxisomes (very long-chain fatty acids, phytanic acid, pristanic acid, and pipecolic acid) and a deficiency of other metabolites whose biosynthesis is dependent upon peroxisomes. An example of the latter category are plasmalogens.

Studies in Zellweger syndrome have also been very important for the resolution of the question of how peroxisomes are synthesized. Furthermore, studies on Zellweger syndrome have laid the basis for the recognition of a large variety of different human diseases in which either peroxisome biogenesis is (partially) impaired or one of its metabolic functions is impaired.