Channel formation by yeast F-ATP synthase and the role of dimerization in the mitochondrial permeability transition

J Biol Chem. 2014 Jun 6;289(23):15980-5. doi: 10.1074/jbc.C114.559633. Epub 2014 May 1.

Abstract

Purified F-ATP synthase dimers of yeast mitochondria display Ca(2+)-dependent channel activity with properties resembling those of the permeability transition pore (PTP) of mammals. After treatment with the Ca(2+) ionophore ETH129, which allows electrophoretic Ca(2+) uptake, isolated yeast mitochondria undergo inner membrane permeabilization due to PTP opening. Yeast mutant strains ΔTIM11 and ΔATP20 (lacking the e and g F-ATP synthase subunits, respectively, which are necessary for dimer formation) display a striking resistance to PTP opening. These results show that the yeast PTP originates from F-ATP synthase and indicate that dimerization is required for pore formation in situ.

Keywords: Calcium; F1FO-ATPase; Ion Channel; Mitochondria; Mitochondrial Permeability Transition (MPT); Oxidative Stress; Yeast.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Dimerization
  • Electrophoresis, Polyacrylamide Gel
  • Mitochondrial Membrane Transport Proteins / chemistry
  • Mitochondrial Membrane Transport Proteins / physiology*
  • Mitochondrial Permeability Transition Pore
  • Mitochondrial Proton-Translocating ATPases / metabolism*
  • Saccharomyces cerevisiae / enzymology*

Substances

  • Mitochondrial Membrane Transport Proteins
  • Mitochondrial Permeability Transition Pore
  • Mitochondrial Proton-Translocating ATPases