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Attenuation of autophagy impacts on muscle fibre development, starvation induced stress and fibre regeneration following acute injury

Paolini, Andrea; Omairi, Saleh; Mitchell, Robert; Vaughan, Danielle; Matsakas, Antonios; Vaiyapuri, Sakthivel; Ricketts, Thomas; Rubinsztein, David C.; Patel, Ketan

Authors

Andrea Paolini

Saleh Omairi

Robert Mitchell

Danielle Vaughan

Antonios Matsakas

Sakthivel Vaiyapuri

Thomas Ricketts

David C. Rubinsztein

Ketan Patel



Abstract

Autophagy has been implicated as a major factor in the development of a number of diseases of skeletal muscle. However, its role in skeletal muscle homeostasis is still evolving. We examined skeletal muscle architecture in a mouse model, Atg16L1, where autophagy is attenuated but importantly still present. We show that muscle fibres from Atg16L1 mice were smaller than wild-type counterparts, proving a role for this process in the growth of these cells. We show that mild attenuation of autophagy results in accelerated muscle loss during the initial phase of acute starvation. Furthermore, we show that regeneration of skeletal muscle following cardiotoxin (CTX) mediated injury is slower in the Atg16L1 mouse compared to wild-type. Lastly, we show that autophagy controls the integrity of the sarcolemma. Attenuated autophagy makes muscle fibres more susceptible to infiltration by circulating immunoglobulins following muscle injury with CTX. These fibres internalise dystrophin and nNOS. Importantly these fibres are able to restore dystrophin and nNOS localisation and do not die. In conclusion, these studies shed new light into the ability of skeletal muscle fibres to cope with injury and establish a link between the fine-tuning of autophagy and skeletal muscle regeneration.

Journal Article Type Article
Journal Scientific Reports
Print ISSN 2045-2322
Electronic ISSN 2045-2322
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 8
Issue 1
Article Number 9062
Institution Citation Paolini, A., Omairi, S., Mitchell, R., Vaughan, D., Matsakas, A., Vaiyapuri, S., …Patel, K. (in press). Attenuation of autophagy impacts on muscle fibre development, starvation induced stress and fibre regeneration following acute injury. Scientific reports, 8(1), https://doi.org/10.1038/s41598-018-27429-7
DOI https://doi.org/10.1038/s41598-018-27429-7
Keywords Autophagy; Proteolysis
Publisher URL https://www.nature.com/articles/s41598-018-27429-7
Copyright Statement Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
© The Author(s) 2018

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Copyright Statement
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
© The Author(s) 2018







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