Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2011) 26 P362

ECE2011 Poster Presentations Adrenal medulla (7 abstracts)

Succinate dehydrogenase (SDH) mutations: biochemical and functional effects in pheochromocytoma/paraganglioma tissues

E Rapizzi 1 , T Ercolino 2 , L Canu 1 , V Giachè 1 & M Mannelli 1


1Department of Clinical Pathophysiology, Section of Endocrinology, University of Florence, Florence, Italy; 2Diagnostic Genetic Unit, Careggi Hospital, Azienda Ospedaliera Universitaria Careggi, Florence, Italy.


Pheochromocytoma (PHEO)/paraganglioma (PGL) are neural crest-derived tumors, and about 25% of the apparently sporadic cases are due to a germ line mutation in one of the susceptibility genes. The group of these genes includes the genes encoding three of the four subunits of the SDH, and the recently discovered gene, SDHAF2/SDH5, responsible for the flavination of the SDHA subunit.

Although several hypotheses have been proposed, the molecular events by which an impaired SDH function causes the onset of these tumors are still unknown.

In the present study, 43 samples of PHEOs and 15 samples of HN-PGLs were evaluated for SDH, citrate synthase (CS) activity, and mitochondrial content.

Our results demonstrate that in tumors of SDH-mutated patients SDH activity is always decreased and that a decreased SDH activity is present also in some wt patients tumors. In any event, the decrement of complex II activity always correlates with a decrease in SDH content. The DNA of all the wt patients with a decreased SDH activity were screened for large deletions and SDHAF2/SDH5 mutations, but resulted wt once again. Interestingly, CS activity was comparable among all the tissues, thus suggesting that mitochondrial function was not aspecifically impaired. The expression of COX, which is another enzyme of the respiratory chain, has been found extremely variable in SDH mutated as well as in SDH-wt and SDH-polymorphic tumoral tissues, while VDAC content, that is a channel present on the outer mitochondrial membrane, was comparable among all the samples.

In conclusion, impairment of SDH activity in SDH-wt tissues suggests that these tumors might be mutated for other still unknown susceptibility genes affecting SDH function.

Moreover, the extreme variability in COX expression levels strongly suggests to evaluate functions and expression of other mitochondrial complexes and enzymes to better understand mitochondrial role in the pathogenesis of these tumors.

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