The tumor suppressor function of mitochondria: translation into the clinics.
Recently, the inevitable metabolic reprogramming experienced by cancer cells as a result of the onset of cellular proliferation has been added to the list of hallmarks of the cancer cell phenotype. Proliferation is bound to the synchronous fluctuation of cycles of an increased glycolysis concurrent with a restrained oxidative phosphorylation. Mitochondria are key players in the metabolic cycling experienced during proliferation because of their essential roles in the transduction of biological energy and in defining the life-death fate of the cell. These two activities are molecularly and functionally integrated and are both targets of commonly altered cancer genes. Moreover, energetic metabolism of the cancer cell also affords a target to develop new therapies because the activity of mitochondria has an unquestionable tumor suppressor function. In this review, we summarize most of these findings paying special attention to the opportunity that translation of energetic metabolism into the clinics could afford for the management of cancer patients. More specifically, we emphasize the role that mitochondrial beta-F1-ATPase has as a marker for the prognosis of different cancer patients as well as in predicting the tumor response to therapy.
Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa, CSIC-UAM and CIBER de Enfermedades Raras (CIBERER), Universidad Autónoma de Madrid, 28049 Madrid, Spain. jmcuezva@cbm.uam.es
José M
JM
Cuezva
Alvaro D
AD
Ortega
Imke
I
Willers
Laura
L
Sánchez-Cenizo
Marcos
M
Aldea
María
M
Sánchez-Aragó
D049109:Cell Proliferation; D004734:Energy Metabolism; D016147:Genes, Tumor Suppressor; D006801:Humans; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology*; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D010085:Oxidative Phosphorylation; D006180:Proton-Translocating ATPases / Q000235:genetics*
D006180:Proton-Translocating ATPases