ATP Synthase C-Subunit-Deficient Mitochondria Have a Small Cyclosporine A-Sensitive Channel, but Lack the Permeability Transition Pore

Maria A. Neginskaya, Maria E. Solesio, Elena V. Berezhnaya, Giuseppe F. Amodeo, Nelli Mnatsakanyan, Elizabeth A. Jonas, Evgeny V. Pavlov

Research output: Contribution to journalArticle

Abstract

Permeability transition (PT) is an increase in mitochondrial inner membrane permeability that can lead to a disruption of mitochondrial function and cell death. PT is responsible for tissue damage in stroke and myocardial infarction. It is caused by the opening of a large conductance (∼1.5 nS) channel, the mitochondrial PT pore (mPTP). We directly tested the role of the c-subunit of ATP synthase in mPTP formation by measuring channel activity in c-subunit knockout mitochondria. We found that the classic mPTP conductance was lacking in c-subunit knockout mitochondria, but channels sensitive to the PT inhibitor cyclosporine A could be recorded. These channels had a significantly lower conductance compared with the cyclosporine A-sensitive channels detected in parental cells and were sensitive to the ATP/ADP translocase inhibitor bongkrekic acid. We propose that, in the absence of the c-subunit, mPTP cannot be formed, and a distinct cyclosporine A-sensitive low-conductance channel emerges.

Original languageEnglish (US)
Pages (from-to)11-17.e2
JournalCell Reports
Volume26
Issue number1
DOIs
StatePublished - Jan 2 2019

Keywords

  • ATP synthase c-subunit
  • HAP1-A12 cells
  • cyclosporine A-sensitive channel
  • patch-clamp
  • permeability transition pore

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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