Parkin Overexpression Attenuates Sepsis-Induced Muscle Wasting

Parkin Overexpression Attenuates Sepsis-Induced Muscle Wasting

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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 oljelampe 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 fleshlight automatique mitochondrial quality and contents.