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.

D'Acunzo, P., Strappazzon, F., Caruana, I., Meneghetti, G., Di Rita, A., Simula, L., Weber, G., Del Bufalo, F., Dalla Valle, L., Campello, S., Locatelli, F., Cecconi, F., Reversible induction of mitophagy by an optogenetic bimodular system, <<NATURE COMMUNICATIONS>>, 2019; 10 (1): 1-13. [doi:10.1038/s41467-019-09487-1] [https://hdl.handle.net/10807/228206]

Reversible induction of mitophagy by an optogenetic bimodular system

Locatelli, Franco
Penultimo
;
Cecconi, Francesco
2019

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.
2019
Inglese
D'Acunzo, P., Strappazzon, F., Caruana, I., Meneghetti, G., Di Rita, A., Simula, L., Weber, G., Del Bufalo, F., Dalla Valle, L., Campello, S., Locatelli, F., Cecconi, F., Reversible induction of mitophagy by an optogenetic bimodular system, <<NATURE COMMUNICATIONS>>, 2019; 10 (1): 1-13. [doi:10.1038/s41467-019-09487-1] [https://hdl.handle.net/10807/228206]
File in questo prodotto:
File Dimensione Formato  
s41467-019-09487-1.pdf

accesso aperto

Licenza: Creative commons
Dimensione 6.27 MB
Formato Adobe PDF
6.27 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/228206
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 23
  • ???jsp.display-item.citation.isi??? 25
social impact