The Saccharomyces cerevisiae mitochondrial unselective channel behaves as a physiological uncoupling system regulated by Ca2+, Mg2+, phosphate and ATP

Alfredo Cabrera-Orefice, Rodrigo Ibarra-García-Padilla, Rocío Maldonado-Guzmán, Sergio Guerrero-Castillo, Luis A. Luévano-Martínez, Victoriano Pérez-Vázquez, Manuel Gutiérrez-Aguilar, Salvador Uribe-Carvajal

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.