Reversible induction of mitophagy by an optogenetic bimodular system
| العنوان: | Reversible induction of mitophagy by an optogenetic bimodular system |
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| المؤلفون: | Anthea Di Rita, Francesca Del Bufalo, Luisa Dalla Valle, Francesco Cecconi, Luca Simula, Gerrit Weber, Franco Locatelli, Ignazio Caruana, Silvia Campello, Flavie Strappazzon, Pasquale D’Acunzo, Giacomo Meneghetti |
| المصدر: | Nature Communications, Vol 10, Iss 1, Pp 1-13 (2019) Nature Communications |
| بيانات النشر: | Nature Portfolio, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Programmed cell death, Settore BIO/06, animal structures, Science, General Physics and Astronomy, 02 engineering and technology, Optogenetics, Mitochondrion, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Mice, Mitophagy, medicine, Animals, Humans, Lymphocytes, lcsh:Science, Zebrafish, Adaptor Proteins, Signal Transducing, Multidisciplinary, biology, Chemistry, HEK 293 cells, Neurotoxicity, Signal Transducing, Adaptor Proteins, Mitochondrial Degradation, General Chemistry, 021001 nanoscience & nanotechnology, biology.organism_classification, medicine.disease, Cell biology, Mitochondria, Cytosol, HEK293 Cells, HeLa Cells, 030104 developmental biology, Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, embryonic structures, mytophagy, lcsh:Q, 0210 nano-technology |
| الوصف: | 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. Autophagic degradation of mitochondria (mitophagy) is a key quality control mechanism in cellular homeostasis, and its misregulation is involved in neurodegenerative diseases. Here the authors develop an optogenetic system for reversible induction of mitophagy and validate its use in cell culture and zebrafish embryos. |
| اللغة: | English |
| تدمد: | 2041-1723 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d3524c1eb3e75ea4cf035447e19a4724Test https://doaj.org/article/20ed3b924c8c43a6a43fe7c1750bfd88Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d3524c1eb3e75ea4cf035447e19a4724 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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