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Updated: Jan 31, 2026

Multi-parameter Measurement of the Permeability Transition Pore Opening in Isolated Mouse Heart Mitochondria
13:42

Multi-parameter Measurement of the Permeability Transition Pore Opening in Isolated Mouse Heart Mitochondria

Published on: September 7, 2012

22.1K

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

Maria A Neginskaya1, Maria E Solesio2, Elena V Berezhnaya1

  • 1College of Dentistry, Department of Basic Sciences, New York University, New York, NY 10010, USA; Laboratory of Molecular Neurobiology, Sothern Federal University, Academy of Biology and Biotechnology, 344090 Rostov-on-Don, Russia.

Cell Reports
|January 4, 2019
PubMed

Insights

Mitochondrial permeability transition (PT) involves a large pore (mPTP). Removing ATP synthase’s c-subunit prevents mPTP formation, suggesting a distinct low-conductance channel emerges.

Area of Science:

  • Mitochondrial physiology and bioenergetics
  • Cellular mechanisms of cell death
  • Cardiovascular and neurological disease pathology

Background:

  • Permeability transition (PT) increases mitochondrial inner membrane permeability, leading to cell death.
  • PT is implicated in tissue damage during stroke and myocardial infarction.
  • The mitochondrial PT pore (mPTP) is a large conductance channel (∼1.5 nS) responsible for PT.

Purpose of the Study:

  • To investigate the role of the c-subunit of ATP synthase in the formation of the mitochondrial PT pore (mPTP).
  • To characterize the channel activity in mitochondria lacking the c-subunit of ATP synthase.

Main Methods:

  • Direct measurement of channel activity in isolated mitochondria.
  • Utilizing c-subunit knockout mitochondria to assess mPTP formation.
  • Electrophysiological recordings of channel conductance.

Main Results:

  • The characteristic large conductance (∼1.5 nS) of the mPTP was absent in c-subunit knockout mitochondria.
  • Cyclosporine A-sensitive channels were detected in knockout mitochondria, but with significantly lower conductance.
  • These low-conductance channels were sensitive to bongkrekic acid, an inhibitor of the ATP/ADP translocase.

Conclusions:

  • The c-subunit of ATP synthase is essential for the formation of the canonical mPTP.
  • In the absence of the c-subunit, a distinct, cyclosporine A-sensitive, low-conductance channel can be activated.
  • This suggests a novel pathway for mitochondrial permeability regulation independent of the classical mPTP.
Keywords:
ATP synthase c-subunitHAP1-A12 cellscyclosporine A-sensitive channelpatch-clamppermeability transition pore

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