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Journal of Bioenergetics and Biomembranes

, Volume 47, Issue 6, pp 477–491 | Cite as

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
Article

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 (ΔΨ), 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.

Keywords

Permeability transition Mitochondrial unselective channel Yeast mitochondria Synergism Physiological uncoupling 

Abbreviations

PT

permeability transition

ScMUC

Saccharomyces cerevisiae Mitochondrial Unselective Channel

PTP

Permeability Transition Pore

ANC

Adenine Nucleotide Carrier

VDAC

Voltage Dependent Anion Channel

PiC

Phosphate Carrier

CCCP

carbonyl cyanide 3-chlorophenylhydrazone

ΔΨ

Transmembrane Potential

ROS

Reactive Oxygen Species

EDTA

Ethylene-diamine-tetra-acetic acid

EGTA

ethylene-glycol-tetra-acetic acid

Notes

Acknowledgments

The authors thank Natalia Chiquete-Félix and Ramón Méndez for technical assistance. Partially funded by CONACYT grant 239487 and PAPIIT-UNAM IN204015. ACO is a CONACYT fellow enrolled in the Biochemistry PhD program at UNAM. LALM is supported by a postdoctoral fellowship from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), process number 2013/04919-9.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Alfredo Cabrera-Orefice
    • 1
  • Rodrigo Ibarra-García-Padilla
    • 1
  • Rocío Maldonado-Guzmán
    • 1
  • Sergio Guerrero-Castillo
    • 2
  • Luis A. Luévano-Martínez
    • 3
  • Victoriano Pérez-Vázquez
    • 4
  • Manuel Gutiérrez-Aguilar
    • 5
  • Salvador Uribe-Carvajal
    • 1
    • 6
  1. 1.Departamento de Genética Molecular, Instituto de Fisiología CelularUniversidad Nacional Autónoma de MéxicoMexico CityMexico
  2. 2.Nijmegen Center for Mitochondrial DisordersNijmegenThe Netherlands
  3. 3.Departamento de Bioquímica, Instituto de QuímicaUniversidade de São PauloSão PauloBrazil
  4. 4.Departamento de Ciencias MédicasUniversidad de GuanajuatoGuanajuatoMexico
  5. 5.Center for Human NutritionWashington University School of MedicineSt. LouisUSA
  6. 6.Salvador Uribe-Carvajal, Department of Molecular GeneticsInstituto de Fisiología CelularMexico CityMexico

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