Reversible induction of mitophagy by an optogenetic bimodular system
- 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.
- Nature communications 10: 1533 (Journal)
- Registered Authors
- Dalla Valle, Luisa
- MeSH Terms
- Adaptor Proteins, Signal Transducing/metabolism
- Adaptor Proteins, Signal Transducing/physiology*
- HEK293 Cells
- HeLa Cells
- 30948710 Full text @ Nat. Commun.
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. (2019) Reversible induction of mitophagy by an optogenetic bimodular system. Nature communications. 10:1533.
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.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes