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Reversible induction of mitophagy by an optogenetic bimodular system

Author

Listed:
  • Pasquale D’Acunzo

    (Oncology and Cell and Gene Therapy, IRCCS Bambino Gesù Children’s Hospital)

  • Flavie Strappazzon

    (IRCCS Fondazione Santa Lucia
    University of Tor Vergata)

  • Ignazio Caruana

    (Oncology and Cell and Gene Therapy, IRCCS Bambino Gesù Children’s Hospital)

  • Giacomo Meneghetti

    (University of Padova)

  • Anthea Di Rita

    (IRCCS Fondazione Santa Lucia
    University of Tor Vergata)

  • Luca Simula

    (Oncology and Cell and Gene Therapy, IRCCS Bambino Gesù Children’s Hospital
    University of Tor Vergata)

  • Gerrit Weber

    (Oncology and Cell and Gene Therapy, IRCCS Bambino Gesù Children’s Hospital)

  • Francesca Del Bufalo

    (Oncology and Cell and Gene Therapy, IRCCS Bambino Gesù Children’s Hospital)

  • Luisa Dalla Valle

    (University of Padova)

  • Silvia Campello

    (IRCCS Fondazione Santa Lucia
    University of Tor Vergata)

  • Franco Locatelli

    (Oncology and Cell and Gene Therapy, IRCCS Bambino Gesù Children’s Hospital
    Sapienza University of Rome)

  • Francesco Cecconi

    (Oncology and Cell and Gene Therapy, IRCCS Bambino Gesù Children’s Hospital
    University of Tor Vergata
    Unit of Cell Stress and Survival, Danish Cancer Society Research Center)

Abstract

Autophagy-mediated degradation of mitochondria (mitophagy) is a key process in cellular quality control. Although mitophagy impairment is involved in several patho-physiological conditions, valuable methods to induce mitophagy with low toxicity in vivo are still lacking. Herein, we describe a new optogenetic tool to stimulate mitophagy, based on light-dependent recruitment of pro-autophagy protein AMBRA1 to mitochondrial surface. Upon illumination, AMBRA1-RFP-sspB is efficiently relocated from the cytosol to mitochondria, where it reversibly mediates mito-aggresome formation and reduction of mitochondrial mass. Finally, as a proof of concept of the biomedical relevance of this method, we induced mitophagy in an in vitro model of neurotoxicity, fully preventing cell death, as well as in human T lymphocytes and in zebrafish in vivo. Given the unique features of this tool, we think it may turn out to be very useful for a wide range of both therapeutic and research applications.

Suggested Citation

  • Pasquale D’Acunzo & Flavie Strappazzon & Ignazio Caruana & Giacomo Meneghetti & Anthea Di Rita & Luca Simula & Gerrit Weber & Francesca Del Bufalo & Luisa Dalla Valle & Silvia Campello & Franco Locate, 2019. "Reversible induction of mitophagy by an optogenetic bimodular system," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09487-1
    DOI: 10.1038/s41467-019-09487-1
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