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Cabrera-Orefice, Alfredo; Ibarra-Garcia-Padilla, Rodrigo; Maldonado-Guzman, Rocio; Guerrero-Castillo, Sergio; Luevano-Martinez, Luis A; Perez-Vazquez, Victoriano; Gutierrez-Aguilar, Manuel; Uribe-Carvajal, Salvador (2015)

THE SACCHAROMYCES CEREVISIAE MITOCHONDRIAL UNSELECTIVE CHANNEL BEHAVES AS A PHYSIOLOGICAL UNCOUPLING SYSTEM REGULATED BY CA2+, MG2+, PHOSPHATE AND ATP

J. Bioenerg. Biomembr. 47(6):477-491
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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.