| Popis: |
Mitochondrial glutathione (mGSH) is critical for cell survival. We recently reported the localization of OGC (SLC25A11) and DIC (SLC25A10) in hRPE. Herein, we investigated the suppression of OGC and DIC and the effect of αB crystallin chaperone peptide co-treatment on RPE cell death and mitochondrial function. Non-polarized and polarized human RPE were co-treated for 24 h with phenyl succinic acid (PS, 5 mM) or butyl malonic acid (BM, 5 mM) with or without αB cry peptide (75 µg/mL). mGSH levels, mitochondrial bioenergetics, and ETC proteins were analyzed. The effect of mGSH depletion on cell death and barrier function was determined in polarized RPE co-treated with PS, OGC siRNA or BM and αB cry peptide. Inhibition of OGC and DIC resulted in a significant decrease in mGSH and increased apoptosis. mGSH depletion significantly decreased mitochondrial respiration, ATP production, and altered ETC protein expression. αB cry peptide restored mGSH, attenuated apoptosis, upregulated ETC proteins, and improved mitochondrial bioenergetics and biogenesis. mGSH transporters exhibited differential polarized localization: DIC (apical) and OGC (apical and basal). Inhibition of mGSH transport compromised barrier function which was partially restored by αB cry peptide. Our findings suggest mGSH augmentation by its transporters may be a valuable approach in AMD therapy. |
