Parkin overexpression attenuates sepsis-induced muscle wasting

Leduc-Gaudet, J. P., Mayaki, D., Reynaud, O., Broering, F. E., Chaffer, T. J., Hussain, S. N. A. et Gouspillou, G. (2020). Parkin overexpression attenuates sepsis-induced muscle wasting. Cells, 9 (6). Article 9061454. ISSN 2073-4409 DOI 10.3390/cells9061454

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Résumé

Sepsis elicits skeletal muscle weakness and fiber atrophy. The accumulation of injured mitochondria and depressed mitochondrial functions are considered as important triggers of sepsis-induced muscle atrophy. It is unclear whether mitochondrial dysfunctions in septic muscles are due to the inadequate activation of quality control processes. We hypothesized that overexpressing Parkin, a protein responsible for the recycling of dysfunctional mitochondria by the autophagy pathway (mitophagy), would confer protection against sepsis-induced muscle atrophy by improving mitochondrial quality and content. Parkin was overexpressed for four weeks in the limb muscles of four-week old mice using intramuscular injections of adeno-associated viruses (AAVs). The cecal ligation and perforation (CLP) procedure was used to induce sepsis. Sham operated animals were used as controls. All animals were studied for 48 h post CLP. Sepsis resulted in major body weight loss and myofiber atrophy. Parkin overexpression prevented myofiber atrophy in CLP mice. Quantitative two-dimensional transmission electron microscopy revealed that sepsis is associated with the accumulation of enlarged and complex mitochondria, an effect which was attenuated by Parkin overexpression. Parkin overexpression also prevented a sepsis-induced decrease in the content of mitochondrial subunits of NADH dehydrogenase and cytochrome C oxidase. We conclude that Parkin overexpression prevents sepsis-induced skeletal muscle atrophy, likely by improving mitochondrial quality and contents.

Type de document:	Article
Mots-clés libres:	Mitochondria Mitochondrial fission Mitochondrial fusion Muscle atrophy Septicemia Parkin Ubiquitin protein ligase Animal C57BL mouse Cecum Complication Gene expression regulation Genetics Ligation Male Metabolism Mitochondrial dynamics Mitochondrion Pathology Sepsis Signal transduction Skeletal muscle cell Animals Mice, Inbred C57BL Muscle Fibers, Skeletal Muscular Atrophy Ubiquitin-Protein Ligases
Date de dépôt:	10 juill. 2023 18:33
Dernière modification:	10 juill. 2023 18:33
Version du document déposé:	Version officielle de l'éditeur
URI:	https://depot-e.uqtr.ca/id/eprint/10705

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