Version 1
: Received: 19 July 2018 / Approved: 19 July 2018 / Online: 19 July 2018 (06:15:58 CEST)
How to cite:
Wang, M.; Lau, L.; Sreekumar, P.G.; Spee, C.; Liu, L.; Hinton, D.R.; Sadda, S.R.; Kannan, R. Characterization of Mitochondrial GSH Transporters and Their Role in RPE Protection. Preprints2018, 2018070346. https://doi.org/10.20944/preprints201807.0346.v1
Wang, M.; Lau, L.; Sreekumar, P.G.; Spee, C.; Liu, L.; Hinton, D.R.; Sadda, S.R.; Kannan, R. Characterization of Mitochondrial GSH Transporters and Their Role in RPE Protection. Preprints 2018, 2018070346. https://doi.org/10.20944/preprints201807.0346.v1
Wang, M.; Lau, L.; Sreekumar, P.G.; Spee, C.; Liu, L.; Hinton, D.R.; Sadda, S.R.; Kannan, R. Characterization of Mitochondrial GSH Transporters and Their Role in RPE Protection. Preprints2018, 2018070346. https://doi.org/10.20944/preprints201807.0346.v1
APA Style
Wang, M., Lau, L., Sreekumar, P.G., Spee, C., Liu, L., Hinton, D.R., Sadda, S.R., & Kannan, R. (2018). Characterization of Mitochondrial GSH Transporters and Their Role in RPE Protection. Preprints. https://doi.org/10.20944/preprints201807.0346.v1
Chicago/Turabian Style
Wang, M., Srinivas R. Sadda and Ram Kannan. 2018 "Characterization of Mitochondrial GSH Transporters and Their Role in RPE Protection" Preprints. https://doi.org/10.20944/preprints201807.0346.v1
Abstract
Mitochondrial dysfunction and oxidative stress are thought to be relevant to the pathogenesis of age-related macular degeneration (AMD). Glutathione (GSH) homeostasis fulfills a number of important roles in mitochondria, such as maintenance of mitochondrial DNA and respiratory competency of cells. Although the transport of mitochondrial GSH (mGSH) is not fully understood, increasing evidence from non-ocular tissues suggests that OGC (2-oxoglutarate carrier, SLC25A11) and DIC (dicarboxylate carrier, SLC25A10) are involved in mGSH transport. However, whether OGC and DIC mediate the transfer of GSH into the mitochondria of retinal pigment epithelial cells (RPE) remains unknown. Thus, we investigated the expression, localization, and function of OGC and DIC in human RPE (hRPE) in relation to oxidative stress and GSH. Both OGC and DIC are expressed in hRPE and are localized in mitochondria. We also found a dose and time-dependent decrease of OGC and DIC expression under oxidative stress and increased expression in polarized RPE. Our data show that the downregulation of OGC and DIC resulted in increased apoptosis and mGSH depletion which can be overcome by co-treatment with GSH-MEE. These findings suggest that overexpression of OGC and DIC may be an effective strategy to decrease susceptibility to mitochondrial toxicants by elevation of mGSH.
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
