Peroxiredoxin 3 and Methionine sulfoxide reductase A are essential for lens cell viability by preserving lens cell mitochondrial function through repair of Cytochrome c.

摘要

The central premise of this dissertation is that mitochondrial antioxidant enzymes are essential to lens cell viability by preserving lens cell mitochondria and protecting and/or repairing lens cell proteins, and two mitochondrial-specific antioxidant enzymes, Peroxiredoxin 3 (PRDX3) and Methionine sulfoxide reductase A (MsrA), are explored. In this dissertation, we will examine the expression of PRDX3 in the human lens, its co-localization to the lens cell mitochondria, its ability to be induced by H2O2-oxidative stress, and speculate how PRDX3 function/s/ could affect the lens. We will also examine the reduced levels of MsrA by targeted gene silencing and its effect on reactive oxygen species production and mitochondrial membrane potential in human lens cells to determine its role in mitochondrial function in the lens. Lastly, we will examine the ability of MsrA to repair and restore function to a critical mitochondrial protein, Cytochrome c. The collective evidence strongly indicates that the loss of mitochondrial-specific enzymes, such as PRDX3 and MsrA, are responsible for increased reactive oxygen species levels, decreased mitochondrial membrane potential, protein aggregation and lens cell death, and further indicates that mitochondrial repair, protective, and reducing systems play key roles in the progression of age-related cataract and other age-related diseases.