Autophagy induction in atrophic muscle cells requires ULK1 activation by TRIM32 through unanchored K63-linked polyubiquitin chains
| Autor: | Fulvio Reggiori, Monica Dentice, Marcella Neri, Manuela Antonioli, M. Di Rienzo, Idil Orhon, Fabiola Ciccosanti, Alessandra Ferlini, Giuseppe Merla, F. Germani, Mauro Piacentini, Barbara Mandriani, H. Ding, Giulia Refolo, Muriel Mari, Maria Teresa Pellico, Marco Corazzari, Molly Kulesz-Martin, Carmela Fusco, Gian Maria Fimia, Yuangang Liu, Alessandra Romagnoli, R. De La Torre |
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| Přispěvatelé: | Center for Liver, Digestive and Metabolic Diseases (CLDM), Microbes in Health and Disease (MHD), Di Rienzo, M., Antonioli, M., Fusco, C., Liu, Y., Mari, M., Orhon, I., Refolo, G., Germani, F., Corazzari, M., Romagnoli, A., Ciccosanti, F., Mandriani, B., Pellico, M. T., De La Torre, R., Ding, H., Dentice, M., Neri, M., Ferlini, A., Reggiori, F., Kulesz-Martin, M., Piacentini, M., Merla, G., Fimia, G. M. |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Plasma protein binding
LS3_11 RNA Small Interfering/metabolism Muscular Dystrophies Myoblasts Tripartite Motif Proteins Limb-Girdle Mice 0302 clinical medicine Ubiquitin Myocyte Autophagy-Related Protein-1 Homolog Autophagy-Related Protein-1 Homolog/metabolism Research Articles adaptor proteins signal transducing animals autophagy-related protein-1 homolog cell line cell transdifferentiation humans lysine mice mice knockout muscular dystrophies limb-girdle myoblasts protein binding rna interference rna small interfering ubiquitin-protein ligases ubiquitination autophagy Mice Knockout Muscular Dystrophies Limb-Girdle/metabolism 0303 health sciences Multidisciplinary biology Chemistry Intracellular Signaling Peptides and Proteins Signal transducing adaptor protein Adaptor Proteins SciAdv r-articles Muscle atrophy Ubiquitin ligase Cell biology 030220 oncology & carcinogenesis RNA Interference medicine.symptom Research Article Signal Transduction Lysine/metabolism Protein Binding Settore BIO/06 Knockout Ubiquitin-Protein Ligases Ubiquitin-Protein Ligases/antagonists & inhibitors Small Interfering NO Cell Line 03 medical and health sciences Adaptor Proteins Signal Transducing/antagonists & inhibitors medicine Autophagy Animals Humans 030304 developmental biology Adaptor Proteins Signal Transducing Lysine Signal Transducing Ubiquitination Cell Biology ULK1 Muscular Dystrophies Limb-Girdle Cell Transdifferentiation biology.protein RNA RNA Small Interfering Atrophy Myoblasts/cytology Transcription Factors |
| Zdroj: | Science Advances, 5(5):8857. AMER ASSOC ADVANCEMENT SCIENCE Di Rienzo, M, Antonioli, M, Fusco, C, Liu, Y, Mari, M, Orhon, I, Refolo, G, Germani, F, Corazzari, M, Romagnoli, A, Ciccosanti, F, Mandriani, B, Pellico, M T, De La Torre, R, Ding, H, Dentice, M, Neri, M, Ferlini, A, Reggiori, F, Kulesz-Martin, M, Piacentini, M, Merla, G & Fimia, G M 2019, ' Autophagy induction in atrophic muscle cells requires ULK1 activation by TRIM32 through unanchored K63-linked polyubiquitin chains ', Science Advances, vol. 5, no. 5, pp. eaau8857 . https://doi.org/10.1126/sciadv.aau8857 Science Advances |
| ISSN: | 2375-2548 |
| DOI: | 10.1126/sciadv.aau8857 |
| Popis: | Muscular dystrophy-associated mutations of TRIM32 impair ULK1-dependent autophagy response during muscle atrophy. Optimal autophagic activity is crucial to maintain muscle integrity, with either reduced or excessive levels leading to specific myopathies. LGMD2H is a muscle dystrophy caused by mutations in the ubiquitin ligase TRIM32, whose function in muscles remains not fully understood. Here, we show that TRIM32 is required for the induction of muscle autophagy in atrophic conditions using both in vitro and in vivo mouse models. Trim32 inhibition results in a defective autophagy response to muscle atrophy, associated with increased ROS and MuRF1 levels. The proautophagic function of TRIM32 relies on its ability to bind the autophagy proteins AMBRA1 and ULK1 and stimulate ULK1 activity via unanchored K63-linked polyubiquitin. LGMD2H-causative mutations impair TRIM32’s ability to bind ULK1 and induce autophagy. Collectively, our study revealed a role for TRIM32 in the regulation of muscle autophagy in response to atrophic stimuli, uncovering a previously unidentified mechanism by which ubiquitin ligases activate autophagy regulators. |
| Databáze: | OpenAIRE |
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