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.

Astragaloside IV alleviates heart failure via activating PPARα to switch glycolysis to fatty acid β-oxidation

“…Mitochondrial biological function plays a vital role in energy production and cellular metabolic functions 15, 16 , and there has been considerable study of the key role played by mitochondrial Ca 2+ uptake in increasing ATP synthesis and stimulating Krebs cycle activity, as well as its involvement in the HF progression 17, 18 . A previous study has shown that the maintenance of optimal mitochondrial function is associated to a great extent with Ca 2+ transport in mitochondrial membranes 16 .…”

The Regulation of Non-Specific Membrane Permeability Transition in Yeast Mitochondria under Oxidative Stress

“…At first glance, such an unexpected result could be explained by the DDC and ATZ inhibition of ∆Ψ generation, presented in all the variants studied, which, in turn, led to the decreased ROS level generated by complexes I and III of the mitochondrial respiratory chain [50]. Cabrera-Orefice and co-authors obtained similar data [46] while studying the regulation of the mitochondrial unselective channel ( Sc MUC) in the S. cerevisiae mitochondria. The authors using AR for peroxide detection showed that a pore inhibitor 4 mM P i increased the ROS generation rate threefold more if the Sc MUC was closed than that if it was open.…”

“…The mechanism of the mPTP complex formation, its architecture, and its composition are under keen discussion and have been studied rather well for animal mitochondria [26][27][28]. Currently, some evident facts defining the phenomenon of mPTP have been obtained: (1) it is CsA-insensitive [29,35,46]; (2) it is inhibited by P i [29,46]; (3) it is induced both upon oxidizing the substrates and in the presence of ATP [29,35,46]; (4) it does not depend completely on Ca 2+ additions [29,46]. Based on the results, we could conclude that the yPTP is not related to any Ca 2+ uptake and differs significantly from the classical and well-defined animal mPTP.…”

Magnesium enhances dehydration tolerance in Schizosaccharomyces pombe by promoting intracellular 5′‐methylthioadenosine accumulation

“…The intracellular increase of magnesium in cells rehydrated in the presence of the ion support the idea that the influx of ions through membranes, without selective permeability, is caused by the influx of rehydrating water. Therefore, the higher intracellular content of a divalent cation such as Mg 2+ might block the mitochondrial unselective channel by forming Mg‐ATP 2− , promoting slow electron flux and leading to a reduction in the respiration rate, as described in the case of S. cerevisiae (Bradshaw & Pfeiffer, ; Cabrera‐Orefice et al, ). This reduction of the respiratory rate may explain the 208 min increase in the λ phase of Schiz.…”