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Gliomas are the most common malignant brain tumors with poor prognosis. The WHO’s classification recognizes isocitrate dehydrogenase 1 ( IDH1 ) mutant astrocytoma and  IDH1 -wildtype glioblastoma (GBM). The  IDH1  mutation confers a survival advantage over the wildtype. There are several explanations for the metabolic advantage of the  IDH1  mutation, some involve mitochondrial implications. Since an ultrastructural comparison of both tumor genotypes is still lacking, we surveyed the ultrastructural effects of the  IDH1  mutation on the mitochondria of the  IDH1 -mutant astrocytoma (n = 15) and  IDH1 -wildtype glioblastoma (n = 15) tumors. Our results show that both  IDH1  genotypes have degenerate and uncoupled mitochondria; this has not been reported before. The presence of ample lipid inclusions and lipid droplets in the cytoplasm of both genotypes support our conclusion of dysfunctional uncoupled mitochondria. Thus, the  IDH1  mutation may have no ultrastructural consequences on the mitochondria, and the aberrant mitochondria in both genotypes may be the result of other unknown mutations. The status of the mitochondria in these genotypes portends a clinical challenge since tumor cells with uncoupled mitochondria are more primitive, aggressive, and considerably treatment resistant.

Comparative survey of mitochondrial ultrastructure in IDH1 -mutant astrocytoma and IDH1 -wildtype glioblastoma (GBM)