Identification of mitochondria translation elongation factor Tu as a contributor to oxidative damage of postburn myocardium

Mitochondrial damage plays an important role in mediating postburn cardiac injury. To elucidate the pivotal mitochondrial proteins and pathways underlying postburn cardiac injury, mitochondria were purified from control and postburn rat hearts. 2-dimensional gel electrophoresis (2-DE) and HPLC-chip-MS/MS analyses revealed 9 differentially expressed proteins, 3 of which were further validated by Western blotting. The differential expression of these mitochondrial proteins was accompanied by increased levels of oxidative cardiac damage and decreased levels of cardiac output. One of the differentially expressed proteins, mitochondria translation elongation factor Tu (EF-Tumt), was hypothesized to contribute crucially to postburn oxidative cardiac damage. The small interfering RNA (siRNA)-mediated downregulation of EF-Tumt in cultured rat cardiomyocytes increased reactive oxygen species (ROS) generation and protein carbonyl levels, and led to cell damage. The potential pathway of this process was associated with respiratory chain complex I deficiency. Together, these results demonstrate the mitochondrial responses to severe burn, and indicate a pathway by which decreased EF-Tumt expression mediates oxidative damage in postburn myocardium.

Graphical abstractFigure optionsDownload full-size imageDownload high-quality image (90 K)Download as PowerPoint slideHighlights► Mitochondria were purified from rat heart by Nycodenz density gradient centrifugation. ► Two-dimensional proteomics revealed 9 differentially expressed mitochondrial proteins. ► Differentially expressed proteins were accompanied by postburn oxidative cardiac damage. ► siRNA-mediated downregulation of EF-Tumt induced oxidative damage in cardiomyocytes. ► The potential mechanism was associated with respiratory chain complex I deficiency.