Mitochondrial energy metabolism and apoptosis regulation in glioblastoma.

Glioblastoma is the most aggressive form of gliomas and is associated with short survival. Recent advancements in molecular genetics resulted in the identification of glioma genomic, epigenomic and transcriptomic hallmarks, and multidimensional data allowed clustering of glioblastomas into molecular subtypes. Parallel with these developments, much scientific attention has been attracted by the exploration of two functional processes linked to mitochondrial regulation. One of these processes involves genomic and mitochondrial gene mutations, mitochondrial protein expression modifications and altered metabolic regulation that define glioblastoma. The second mitochondrially-centered process involves complex molecular interactions and pathways that influence the extrinsic or the intrinsic mechanisms of apoptosis regulation and may underlie the uncontrolled spreading, recurrence and drug resistance of glioblastoma. While the available data are not yet comprehensive, these two complex processes represent important aspects of tumor cell biology, which may provide complementary opportunities for therapeutic manipulations of this highly resistant tumor type.