Mitochondrial membranes contribute to the intracellular compartmentation between mitochondria and the cytosol in eukaryotic cells. Thus, a set of mitochondrial membrane proteins as well as soluble proteins is involved in the channeling of metabolites, ions and water across mitochondrial membranes. An increasing body of literature suggests that these proteins behave as control point in oncology. For example they can be involved (i) in the metabolic shift of cancer cells from oxidative phosphorylation to glycolysis via its binding to other proteins such as Hexokinase II (i.e. Warburg effect), (ii) in the control of calcium fluxes between the ER and the mitochondrion via interaction with the IP3R, (iii) in the control of transmembrane inner potential via interaction with tubulin and finally, (iv) in the regulation of mitochondrial membrane permeability via interaction with Bax/Bcl-2 family members and/or the mitochondrial permeability transition pore. Moreover, some proteins via a shift in their expression appear to be critical for the cancer cell response to chemotherapy (e.g. cisplatin). However, how these diverse functions are modulated and coordinated in cancer cells to control the balance between life and death is still largely unknown and requires extensive review and discussion to update our view of the role of mitochondrial proteins in oncology.

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