The mitochondrial permeability transition pore: Channel formation by F-ATP synthase, integration in signal transduction, and role in pathophysiology

Paolo Bernardi, Andrea Rasola, Michael Forte, Giovanna Lippe

Research output: Contribution to journalArticle

270 Scopus citations

Abstract

The mitochondrial permeability transition (PT) is a permeability increase of the inner mitochondrial membrane mediated by a channel, the permeability transition pore (PTP). After a brief historical introduction, we cover the key regulatory features of the PTP and provide a critical assessment of putative protein components that have been tested by genetic analysis. The discovery that under conditions of oxidative stress the F-ATP synthases of mammals, yeast, and Drosophila can be turned into Ca2+-dependent channels, whose electrophysiological properties match those of the corresponding PTPs, opens new perspectives to the field. We discuss structural and functional features of F-ATP synthases that may provide clues to its transition from an energy-conserving into an energy-dissipating device as well as recent advances on signal transduction to the PTP and on its role in cellular pathophysiology.

Original languageEnglish (US)
Pages (from-to)1111-1155
Number of pages45
JournalPhysiological Reviews
Volume95
Issue number4
DOIs
StatePublished - Oct 1 2015

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Physiology (medical)

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