title: The Saccharomyces cerevisiae mitochondrial unselective channel behaves as a physiological uncoupling system regulated by Ca2+, Mg2+, phosphate and ATP.
abstract: It is proposed that the Saccharomyces cerevisiae the Mitochondrial Unselective Channel ((Sc)MUC) is tightly regulated constituting a physiological uncoupling system that prevents overproduction of reactive oxygen species (ROS). Mg(2+), Ca(2+) or phosphate (Pi) close (Sc)MUC, while ATP or a high rate of oxygen consumption open it. We assessed (Sc)MUC activity by measuring in isolated mitochondria the respiratory control, transmembrane potential (ΔΨ), swelling and production of ROS. At increasing [Pi], less [Ca(2+)] and/or [Mg(2+)] were needed to close (Sc)MUC or increase ATP synthesis. The Ca(2+)-mediated closure of (Sc)MUC was prevented by high [ATP] while the Mg(2+) or Pi effect was not. When Ca(2+) and Mg(2+) were alternatively added or chelated, (Sc)MUC opened and closed reversibly. Different effects of Ca(2+) vs Mg(2+) effects were probably due to mitochondrial Mg(2+) uptake. Our results suggest that (Sc)MUC activity is dynamically controlled by both the ATP/Pi ratio and divalent cation fluctuations. It is proposed that the reversible opening/closing of (Sc)MUC leads to physiological uncoupling and a consequent decrease in ROS production.
authors.affiliation: Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Cabrera-Orefice
authors.affiliation: Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Ibarra-García-Padilla
authors.affiliation: Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico.
authors.forename: Rocío
authors.initials: R
authors.lastname: Maldonado-Guzmán
authors.affiliation: Nijmegen Center for Mitochondrial Disorders, 6500, HB, Nijmegen, The Netherlands.
authors.forename: Sergio
authors.initials: S
authors.lastname: Guerrero-Castillo
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Luévano-Martínez
authors.affiliation: Departamento de Ciencias Médicas, Universidad de Guanajuato, 37320, Guanajuato, León, Mexico.
authors.forename: Victoriano
authors.initials: V
authors.lastname: Pérez-Vázquez
authors.affiliation: Center for Human Nutrition, Washington University School of Medicine, St. Louis, MO, 63110, USA.
authors.forename: Manuel
authors.initials: M
authors.lastname: Gutiérrez-Aguilar
authors.affiliation: Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico. suribe@ifc.unam.mx.|Salvador Uribe-Carvajal, Department of Molecular Genetics, Instituto de Fisiología Celular, UNAM, Apdo. postal 70-242, 04510, Mexico City, Mexico. suribe@ifc.unam.mx.
authors.forename: Salvador
authors.initials: S
authors.lastname: Uribe-Carvajal
mesh_terms: D000255:Adenosine Triphosphate; D002118:Calcium / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*
chemical_list: D000255:Adenosine Triphosphate; D010744:Phosphoric Monoester Hydrolases; D008274:Magnesium; D002118:Calcium
keywords: Mitochondrial unselective channel; Permeability transition; Physiological uncoupling; Synergism; Yeast mitochondria