PKA Phosphorylates the ATPase Inhibitory Factor 1 and Inactivates Its Capacity to Bind and Inhibit the Mitochondrial H+-ATP Synthase
Entity
UAM. Departamento de Biología MolecularPublisher
ElsevierDate
2015-09-29Citation
10.1016/j.celrep.2015.08.052
Cell Reports 12.12 (2015): 2143-2155
ISSN
2211-1247DOI
10.1016/j.celrep.2015.08.052Funded by
J.G.-B. and C.N-T. were supported by pre-doctoral fellowships from FPI-MICINN/MINECO and Fondo Social Europeo, Spain. This work was supported by grants from Ministerio de Economía y Competitividad (SAF2013- 41945-R), Comunidad de Madrid (S2011/BMD-2402), and Fundación Ramon Areces (FRA), Spain. The CBMSO received an institutional grant from the FRAProject
Gobierno de España. SAF2013- 41945-R; Comunidad de Madrid. S2011/BMD-2402/MITOLABEditor's Version
http://dx.doi.org/10.1016/j.celrep.2015.08.052Subjects
Adenosine triphosphate; Protein IF1; Mitochondria; Mitochondrial proton-translocating ATPases; Protein kinases; Biología y Biomedicina / BiologíaRights
© 2015 The Authors
Esta obra está bajo una licencia de Creative Commons Reconocimiento-NoComercial-SinObraDerivada 4.0 Internacional.
Abstract
The mitochondrial H+-ATP synthase synthesizes most of cellular ATP requirements by oxidative phosphorylation (OXPHOS). The ATPase Inhibitory Factor 1 (IF1) is known to inhibit the hydrolase activity of the H+-ATP synthase in situations that compromise OXPHOS. Herein, we demonstrate that phosphorylation of S39 in IF1 by mitochondrial protein kinase A abolishes its capacity to bind the H+-ATP synthase. Only dephosphorylated IF1 binds and inhibits both the hydrolase and synthase activities of the enzyme. The phosphorylation status of IF1 regulates the flux of aerobic glycolysis and ATP production through OXPHOS in hypoxia and during the cell cycle. Dephosphorylated IF1 is present in human carcinomas. Remarkably, mouse heart contains a large fraction of dephosphorylated IF1 that becomes phosphorylated and inactivated upon in vivo β-adrenergic stimulation. Overall, we demonstrate the essential function of the phosphorylation of IF1 in regulating energy metabolism and speculate that dephosho-IF1 might play a role in signaling mitohormesis
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Google Scholar:García-Bermúdez, Javier
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Sánchez-Aragó, María
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Soldevilla, Beatriz
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Nuevo-Tapioles, Cristina
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Cuezva Marcos, José Manuel
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Del Arco, Araceli
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