Energy and metabolic alterations in predisposition to pheochromocytomas and paragangliomas: the so-called Warburg (and more) effect, 15 years on
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Unit for Preventive Medicine, University Medical Center, Albert‐Ludwigs‐University, Hugstetter Straße 55, D‐79106 Freiburg, Germany
1Department of Internal Medicine, Sector of Endocrinology, Erasmus Medical Center, Rotterdam, The Netherlands
- Correspondence should be addressed to H P H Neumann; Email: hartmut.neumann{at}uniklinik-freiburg.de
It happened in Pittsburgh, Pennsylvania, USA, in the year 2000. Bora Baysal, MD, PhD, a Turkish molecular biologist and trained pathologist, collaborated with physicians from Leiden, The Netherlands, who took care of the famous and etiologically puzzling Dutch paraganglioma family. He and his collaborators mapped the susceptibility gene locus to 11q23 and linked it to a gene encoding one of the four subunits of succinate dehydrogenase (mitochondrial complex II, SDHD), an enzyme that lies at the all-important crossroads of energy production, the Krebs tricarboxylic acid cycle and the glycolytic chain. The bombshell was dropped in the journal Science 15 years ago (Baysal et al. 2000). Paraganglioma syndrome ‘type 1’ (PGL1) finally had a genetic etiology: germline mutations of the SDHD gene. Within months, the SDH components B and C (together with SDHD umbrellaed under SDHx) were shown to predispose to similar tumors, if the respective genes (SDHB and SDHC) were mutated (Niemann & Müller 2000, Astuti et al. 2001). Soon there was evidence that not only head and neck paragangliomas but also pheochromocytomas and paragangliomas of the retroperitoneum and chest were caused by germline mutations of these genes (Gimm et al. 2000, Eng et al. 2003). These paradigm-shifting discoveries led to an onslaught, which continues today, of multiple studies …
