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Defining the molecular mechanisms of the mitochondrial permeability transition through genetic manipulation of F-ATP synthase

Author

Listed:
  • Andrea Carrer

    (University of Padova)

  • Ludovica Tommasin

    (University of Padova)

  • Justina Šileikytė

    (Vollum Institute, Oregon Health and Science University)

  • Francesco Ciscato

    (University of Padova)

  • Riccardo Filadi

    (University of Padova
    Consiglio Nazionale delle Ricerche Neuroscience Institute)

  • Andrea Urbani

    (University of Padova)

  • Michael Forte

    (Vollum Institute, Oregon Health and Science University)

  • Andrea Rasola

    (University of Padova)

  • Ildikò Szabò

    (Consiglio Nazionale delle Ricerche Neuroscience Institute
    University of Padova)

  • Michela Carraro

    (University of Padova)

  • Paolo Bernardi

    (University of Padova
    Consiglio Nazionale delle Ricerche Neuroscience Institute)

Abstract

F-ATP synthase is a leading candidate as the mitochondrial permeability transition pore (PTP) but the mechanism(s) leading to channel formation remain undefined. Here, to shed light on the structural requirements for PTP formation, we test cells ablated for g, OSCP and b subunits, and ρ0 cells lacking subunits a and A6L. Δg cells (that also lack subunit e) do not show PTP channel opening in intact cells or patch-clamped mitoplasts unless atractylate is added. Δb and ΔOSCP cells display currents insensitive to cyclosporin A but inhibited by bongkrekate, suggesting that the adenine nucleotide translocator (ANT) can contribute to channel formation in the absence of an assembled F-ATP synthase. Mitoplasts from ρ0 mitochondria display PTP currents indistinguishable from their wild-type counterparts. In this work, we show that peripheral stalk subunits are essential to turn the F-ATP synthase into the PTP and that the ANT provides mitochondria with a distinct permeability pathway.

Suggested Citation

  • Andrea Carrer & Ludovica Tommasin & Justina Šileikytė & Francesco Ciscato & Riccardo Filadi & Andrea Urbani & Michael Forte & Andrea Rasola & Ildikò Szabò & Michela Carraro & Paolo Bernardi, 2021. "Defining the molecular mechanisms of the mitochondrial permeability transition through genetic manipulation of F-ATP synthase," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25161-x
    DOI: 10.1038/s41467-021-25161-x
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