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The cristae modulator Optic atrophy 1 requires mitochondrial ATP synthase oligomers to safeguard mitochondrial function

Author

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  • Rubén Quintana-Cabrera

    (Venetian Institute of Molecular Medicine
    University of Padua
    Institute of Functional Biology and Genomics
    Institute of Biomedical Research of Salamanca, University Hospital of Salamanca, University of Salamanca, CSIC)

  • Charlotte Quirin

    (Venetian Institute of Molecular Medicine
    University of Padua)

  • Christina Glytsou

    (Venetian Institute of Molecular Medicine
    University of Padua
    Department of Pathology, NYU School of Medicine)

  • Mauro Corrado

    (Venetian Institute of Molecular Medicine
    University of Padua
    Max Planck Institute of Immunology and Epigenetics)

  • Andrea Urbani

    (University of Padua)

  • Anna Pellattiero

    (Venetian Institute of Molecular Medicine
    University of Padua)

  • Enrique Calvo

    (Centro Nacional de Investigaciones Cardiovasculares Carlos III)

  • Jesús Vázquez

    (Centro Nacional de Investigaciones Cardiovasculares Carlos III)

  • José Antonio Enríquez

    (Centro Nacional de Investigaciones Cardiovasculares Carlos III
    Institute of Health Carlos III)

  • Christoph Gerle

    (Osaka University
    Japan Science and Technology Agency)

  • María Eugenia Soriano

    (Consiglio Nazionale delle Ricerche)

  • Paolo Bernardi

    (University of Padua
    Consiglio Nazionale delle Ricerche)

  • Luca Scorrano

    (Venetian Institute of Molecular Medicine
    University of Padua)

Abstract

It is unclear how the mitochondrial fusion protein Optic atrophy 1 (OPA1), which inhibits cristae remodeling, protects from mitochondrial dysfunction. Here we identify the mitochondrial F1Fo-ATP synthase as the effector of OPA1 in mitochondrial protection. In OPA1 overexpressing cells, the loss of proton electrochemical gradient caused by respiratory chain complex III inhibition is blunted and this protection is abolished by the ATP synthase inhibitor oligomycin. Mechanistically, OPA1 and ATP synthase can interact, but recombinant OPA1 fails to promote oligomerization of purified ATP synthase reconstituted in liposomes, suggesting that OPA1 favors ATP synthase oligomerization and reversal activity by modulating cristae shape. When ATP synthase oligomers are genetically destabilized by silencing the key dimerization subunit e, OPA1 is no longer able to preserve mitochondrial function and cell viability upon complex III inhibition. Thus, OPA1 protects mitochondria from respiratory chain inhibition by stabilizing cristae shape and favoring ATP synthase oligomerization.

Suggested Citation

  • Rubén Quintana-Cabrera & Charlotte Quirin & Christina Glytsou & Mauro Corrado & Andrea Urbani & Anna Pellattiero & Enrique Calvo & Jesús Vázquez & José Antonio Enríquez & Christoph Gerle & María Eugen, 2018. "The cristae modulator Optic atrophy 1 requires mitochondrial ATP synthase oligomers to safeguard mitochondrial function," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05655-x
    DOI: 10.1038/s41467-018-05655-x
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