Comelli 2017 J Bioenerg Biomembr
|Comelli M, Pretis I, Buso A, Mavelli I (2017) Mitochondrial energy metabolism and signalling in human glioblastoma cell lines with different PTEN gene status. J Bioenerg Biomembr 50:33-52.|
Abstract: Glioblastomas epidemiology and aggressiveness demand for a well characterization of biochemical mechanisms of the cells. The discovery of oxidative tumours related to chemoresistance is changing the prevalent view of dysfunctional mitochondria in cancer cells. Thus, glioblastomas metabolism is now an area of intense research, wherein was documented a high heterogeneity in energy metabolism and in particular in mitochondrial OxPhos. We report results gained by investigating mitochondrial OxPhos and bioenergetics, in a model of three human glioblastoma cell lines characterized by a different PTEN gene status. Functional data are analysed in relation to the expression levels of some main transcription factors and signalling proteins, which can be involved in the regulation of mitochondrial biogenesis and activity. Collectively, our observations indicate for the three cell lines a similar bioenergetic phenotype maintaining a certain degree of mitochondrial oxidative activity, with some difference for PTEN-wild type SF767 cells respect to PTEN-deleted A172 and U87MG characterized by a loss-of-function point mutation of PTEN. SF767 has lower ATP content and higher ADP/ATP ratio, higher AMPK activating-phosphorylation evoking energy impairment, higher OxPhos complexes and PGC1α-Sirt3-p53 protein abundance, in line with a higher respiration. Finally, SF767 shows a similar mitochondrial energy supply, but higher non-phosphorylating respiration linked to dissipation of protonmotive force. Intriguingly, it is now widely accepted that a regulated mitochondrial proton leak attenuate ROS generation and in tumours may be at the base of pro-survival advantage and chemoresistance.
• Keywords: Bioenergetic phenotype, Cancer metabolism, High-resolution respirometry, Human glioblastoma cell lines, Mitochondria-related signalling proteins, Seahorse XFe24 • Bioblast editor: Kandolf G • O2k-Network Lab: IT Udine Grassi B, IT Udine Mavelli I
Labels: MiParea: Respiration, mt-Biogenesis;mt-density Pathology: Cancer
Organism: Human Tissue;cell: Nervous system Preparation: Intact cells, Permeabilized cells Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase
Coupling state: LEAK, ROUTINE, OXPHOS, ET Pathway: N, Gp, CIV, NS, ROX HRR: Oxygraph-2k