Reversible induction of mitophagy by an optogenetic bimodular system

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1533
JournalNature Communications
Volume10
Issue number1
DOIs
Publication statusPublished - Apr 4 2019

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Mitochondrial Degradation
Optogenetics
Mitochondria
mitochondria
induction
T-cells
lymphocytes
impairment
Cell death
quality control
death
toxicity
Quality control
Autophagy
Toxicity
Lighting
illumination
degradation
proteins
Degradation

Cite this

@article{89e9348e53884f41adc64af7d3a484f3,
title = "Reversible induction of mitophagy by an optogenetic bimodular system",
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.",
author = "Pasquale D'Acunzo and Flavie Strappazzon and Ignazio Caruana and Giacomo Meneghetti and {Di Rita}, Anthea and Luca Simula and Gerrit Weber and {Del Bufalo}, Francesca and {Dalla Valle}, Luisa and Silvia Campello and Franco Locatelli and Francesco Cecconi",
year = "2019",
month = "4",
day = "4",
doi = "10.1038/s41467-019-09487-1",
language = "English",
volume = "10",
pages = "1533",
journal = "Nature Communications",
issn = "2041-1723",
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TY - JOUR

T1 - Reversible induction of mitophagy by an optogenetic bimodular system

AU - D'Acunzo, Pasquale

AU - Strappazzon, Flavie

AU - Caruana, Ignazio

AU - Meneghetti, Giacomo

AU - Di Rita, Anthea

AU - Simula, Luca

AU - Weber, Gerrit

AU - Del Bufalo, Francesca

AU - Dalla Valle, Luisa

AU - Campello, Silvia

AU - Locatelli, Franco

AU - Cecconi, Francesco

PY - 2019/4/4

Y1 - 2019/4/4

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-019-09487-1

DO - 10.1038/s41467-019-09487-1

M3 - Article

VL - 10

SP - 1533

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

ER -