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 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

Fingerprint

Mitochondria
Cyclosporine
Permeability
Adenosine Triphosphate
Bongkrekic Acid
ATP Translocases Mitochondrial ADP
Mitochondrial Proton-Translocating ATPases
Cell death
Mitochondrial Membranes
Tissue
Membranes
Cell Death
Stroke
Myocardial Infarction

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

ATP Synthase C-Subunit-Deficient Mitochondria Have a Small Cyclosporine A-Sensitive Channel, but Lack the Permeability Transition Pore. / Neginskaya, Maria A.; Solesio, Maria E.; Berezhnaya, Elena V.; Amodeo, Giuseppe F.; Mnatsakanyan, Nelli; Jonas, Elizabeth A.; Pavlov, Evgeny.

In: Cell Reports, Vol. 26, No. 1, 02.01.2019, p. 11-17.e2.

Research output: Contribution to journalArticle

Neginskaya, Maria A. ; Solesio, Maria E. ; Berezhnaya, Elena V. ; Amodeo, Giuseppe F. ; Mnatsakanyan, Nelli ; Jonas, Elizabeth A. ; Pavlov, Evgeny. / ATP Synthase C-Subunit-Deficient Mitochondria Have a Small Cyclosporine A-Sensitive Channel, but Lack the Permeability Transition Pore. In: Cell Reports. 2019 ; Vol. 26, No. 1. pp. 11-17.e2.
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