Lack of compensatory mitophagy in skeletal muscles during sepsis


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Sedraoui, S., Leduc-Gaudet, J.-P., Mayaki, D., Moamer, A., Huck, L., Gouspillou, G., Petrof, B. J. et Hussain, S. (2024). Lack of compensatory mitophagy in skeletal muscles during sepsis. The Journal of Physiology . ISSN 0022-3751 1469-7793 DOI 10.1113/JP286216

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Skeletal muscle dysfunction is a major problem in critically ill patients suffering from sepsis. This condition is associated with mitochondrial dysfunction and increased autophagy in skeletal muscles. Autophagy is a proteolytic mechanism involved in eliminating dysfunctional cellular components, including mitochondria. The latter process, referred to as mitophagy, is essential for maintaining mitochondrial quality and skeletal muscle health. Recently, a fluorescent reporter system called mito-QC (i.e. mitochondrial quality control) was developed to specifically quantify mitophagy levels. In the present study, we used mito-QC transgenic mice and confocal microscopy to morphologically monitor mitophagy levels during sepsis. To induce sepsis, Mito-QC mice received Escherichia coli lipopolysaccharide (10 mg kg–1 i.p.) or phosphate-buffered saline and skeletal muscles (hindlimb and diaphragm) were excised 48 h later. In control groups, there was a negative correlation between the basal mitophagy level and overall muscle mitochondrial content. Sepsis increased general autophagy in both limb muscles and diaphragm but had no effect on mitophagy levels. Sepsis was associated with a downregulation of certain mitophagy receptors (Fundc1, Bcl2L13, Fkbp8 and Phbb2). The present study suggests that general autophagy and mitophagy can be dissociated from one another, and that the characteristic accumulation of damaged mitochondria in skeletal muscles under the condition of sepsis may reflect a failure of adequate compensatory mitophagy.

Key points
- There was a negative correlation between the basal level of skeletal muscle mitophagy and the mitochondrial content of individual muscles.
- Mitophagy levels in limb muscles and the diaphragm were unaffected by lipopolysaccharide (LPS)-induced sepsis.
- With the exception of BNIP3 in sepsis, LPS administration induced either no change or a downregulation of mitophagy receptors in skeletal muscles.

Type de document: Article
Date de dépôt: 17 juin 2024 13:24
Dernière modification: 17 juin 2024 13:24
Version du document déposé: Version officielle de l'éditeur

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