We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Parkin Overexpression Attenuates Sepsis-Induced Muscle Wasting.
- Authors
Leduc-Gaudet, Jean-Philippe; Mayaki, Dominique; Reynaud, Olivier; Broering, Felipe E.; Chaffer, Tomer J.; Hussain, Sabah N. A.; Gouspillou, Gilles
- Abstract
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.
- Subjects
SKELETAL muscle; MITOCHONDRIAL membranes; NADH dehydrogenase; CYTOCHROME oxidase; MUSCLES; INTRAMUSCULAR injections; TRANSMISSION electron microscopy; SEPSIS
- Publication
Cells (2073-4409), 2020, Vol 9, Issue 6, p1454
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells9061454