Sepsis Dysregulates Mitochondrial microRNA and Biogenesis in the Diaphragm but Not Limb Muscle

Diaphragm dysfunction that leads to respiratory failure is a significant clinical consequence of sepsis-induced critical illness. Diaphragm muscle weakness contributes to morbidity and mortality in these individuals in part due to impaired mitochondrial function. Restoring normal mitochondrial biogenesis is associated with improved survival and physical function. Therefore, identifying reliable biomarkers of mitochondrial dysfunction in diaphragm muscle will allow for more focused and targeted interventions designed to improve the morbidity of critically ill patients. We used a rodent cecal-ligation and puncture (CLP) model to mimic a moderate grade of sepsis. The diaphragm muscle was harvested from adult mice 48 h following CLP (n = 6) or a sham CLP procedure (n = 6). Our primary finding was that moderate grade CLP increases expression of mitochondria-associated microRNA in the diaphragm. Correspondingly, genes associated with mitochondrial biogenesis decreased. Our study provides evidence for sepsis-mediated dysregulation of mitochondrial homeostasis. This may play a role in diaphragm muscle dysfunction, respiratory failure, and difficult weaning from mechanical ventilation in sepsis-induced critical illness.