title: The inhibitor protein (IF1) of the F1F0-ATPase modulates human osteosarcoma cell bioenergetics.
abstract: The bioenergetics of IF1 transiently silenced cancer cells has been extensively investigated, but the role of IF1 (the natural inhibitor protein of F1F0-ATPase) in cancer cell metabolism is still uncertain. To shed light on this issue, we established a method to prepare stably IF1-silenced human osteosarcoma clones and explored the bioenergetics of IF1 null cancer cells. We showed that IF1-silenced cells proliferate normally, consume glucose, and release lactate as controls do, and contain a normal steady-state ATP level. However, IF1-silenced cells displayed an enhanced steady-state mitochondrial membrane potential and consistently showed a reduced ADP-stimulated respiration rate. In the parental cells (i.e. control cells containing IF1) the inhibitor protein was found to be associated with the dimeric form of the ATP synthase complex, therefore we propose that the interaction of IF1 with the complex either directly, by increasing the catalytic activity of the enzyme, or indirectly, by improving the structure of mitochondrial cristae, can increase the oxidative phosphorylation rate in osteosarcoma cells grown under normoxic conditions.
authors.affiliation: From the Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Via Irnerio 48, 40126 Bologna, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Barbato
authors.affiliation: From the Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Via Irnerio 48, 40126 Bologna, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Sgarbi
authors.affiliation: From the Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Via Irnerio 48, 40126 Bologna, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Gorini
authors.affiliation: From the Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Via Irnerio 48, 40126 Bologna, Italy alessandra.baracca@unibo.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Baracca
authors.affiliation: From the Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Via Irnerio 48, 40126 Bologna, Italy giancarlo.solaini@unibo.it.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Solaini
mesh_terms: D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004734:Energy Metabolism / Q000235:genetics; D020868:Gene Silencing; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000235:genetics; D025261:Mitochondrial Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000235:genetics*; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010085:Oxidative Phosphorylation; D011506:Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D034741:RNA, Small Interfering; D000097795:ATPase Inhibitory Protein
chemical_list: D025261:Mitochondrial Proton-Translocating ATPases; D011506:Proteins; D034741:RNA, Small Interfering; D000097795:ATPase Inhibitory Protein; C474451:F1F0-ATP synthase
keywords: ATP Synthase; Bioenergetics; Cancer; F1F0-ATPase; IF1; Metabolism; Mitochondria; Oxidative Phosphorylation