Electron microscopy morphology of the mitochondrial network in gliomas and their vascular microenvironment

Gliomas still represent a serious and discouraging brain tumor; despite of the diversity of therapeutic modalities, the prognosis for patients is still poor. Understanding the structural and functional characteristics of the vascular microenvironment in gliomas is essential for the design of future therapeutic strategies. This review describes and analyzes the electron microscopy morphology of the mitochondrial network in human gliomas and their vascular microenvironment. Heterogeneous mitochondrial network alterations in glioma cells and in microvascular environment are implicated directly and indirectly in the processes linked to hypoxia-tolerant and hypoxia-sensitive cells phenotype, effects of the hypoxia-inducible factor-1α, increased expression of several glycolytic protein isoforms as well as fatty acid synthase, and survivin. The prevalent existence of partial or total cristolysis observed suggests that oxidative phosphorylation is severely compromised. A mixed therapy emerged as the most appropriate. This article is part of a Special Issue entitled: Bioenergetics of Cancer.

Research Highlights► Mitochondrial network is highly heterogeneous; this fact is related with the cellular variability of astrocytomas and variations in microenvironment conditions. ► The prevalent existence of partial or total cristolysis suggests that the ability of human astrocytomas to generate ATP by mitochondrial oxidative phosphorylation would be severely compromised. ► In some astrocytoma cells, a predominant presence of mitochondria with dense matrix displayed in closed groups exists; in other, the principal finding is the lucent-swelling mitochondria with disarrangement and distortion of cristae and partial or total cristolysis. ► Mitochondria are implicated directly and indirectly in the processes linked to hypoxia-tolerant and hypoxia-sensitive cells phenotype, effects of the HIF-1α, increased expression of glycolytic protein isoforms, fatty acid synthase, and survivin, consequently a mixed therapy emerged as the most appropriate.