From Cancer, Malate–Aspartate Shuttle, RNA Replicase, and mtDNA to Trypanosomes and Back to Cancer Again

I studied medicine to become an endocrinologist but ended up in biochemistry. As a graduate student, I studied tumor mitochondria and discovered the malate–aspartate shuttle (the major route in animal cells for shuttling reducing equivalents into mitochondria). As a postdoc in New York, I switched to the replication of RNA bacteriophages, and on my return to Amsterdam, I started on mitochondrial biogenesis and discovered the circular mitochondrial DNAs (mtDNAs) of animal mitochondria and yeast. I also tackled trypanosomatids, major parasites of humans, in which we characterized their exotic mtDNA networks and discovered the glycosome, an organelle containing most of the glycolytic system. We helped to unravel the mechanism of antigenic variation in African trypanosomes and even discovered a new base, base J, in the DNA of trypanosomatids. After moving to the Netherlands Cancer Institute, I combined the trypanosomatids with a project on mechanisms of multidrug resistance in cancer cells. In particular, studying mice with one or more disrupted ABC transporter genes resulted in interesting findings in drug pharmacokinetics and in the elucidation of the cause of two inborn errors.