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

Author(s)

Cabrera-Orefice, Alfredo ^[1] ; Ibarra-Garcia-Padilla, Rodrigo ^[1] ; Maldonado-Guzman, Rocio ^[1] ; Guerrero-Castillo, Sergio ^[2] ; Luevano-Martinez, Luis A. ^[3] ; Perez-Vazquez, Victoriano ^[4] ; Gutierrez-Aguilar, Manuel ^[5] ; Uribe-Carvajal, Salvador ^{[1, 6]}

Affiliation

^[1] Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Dept Mol Genet, Mexico City 04510, DF - Mexico

^[2] Nijmegen Ctr Mitochondrial Disorders, NL-6500 HB Nijmegen - Netherlands

^[3] Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-01498 Sao Paulo, SP - Brazil

^[4] Univ Guanajuato, Dept Ciencias Med, Guanajuato 37320, Leon - Mexico

^[5] Washington Univ, Sch Med, Ctr Human Nutr, St Louis, MO 63110 - USA

^[6] Univ Nacl Autonoma Mexico, Dept Mol Genet, Inst Fisiol Celular, Salvador Uribe Carvajal, Mexico City 04510, DF - Mexico

• Document type: Journal article
• Source: Journal of Bioenergetics and Biomembranes; v. 47, n. 6, p. 477-491, DEC 2015.
• Web of Science Citations: 3

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). Mg2+, Ca2+ 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 (Delta I), swelling and production of ROS. At increasing {[}Pi], less {[}Ca2+] and/or {[}Mg2+] were needed to close (Sc) MUC or increase ATP synthesis. The Ca2+-mediated closure of (Sc) MUC was prevented by high {[}ATP] while the Mg2+ or Pi effect was not. When Ca2+ and Mg2+ were alternatively added or chelated, (Sc) MUC opened and closed reversibly. Different effects of Ca2+ vs Mg2+ effects were probably due to mitochondrial Mg2+ 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. (AU)

• FAPESP's process: 13/04919-9 - Evaluation of the adaptive response of mitochondrial membranes to stress: role of cardiolipin in membrane plasticity, dynamics and pathological situations
• Grantee: Luis Alberto Luevano Martinez
• Support Opportunities: Scholarships in Brazil - Post-Doctoral