Depletion of Mitochondrial DNA in Differentiated Retinal Pigment Epithelial Cells
| Autor: | Melissa A. Calton, Shibo Tang, Douglas Vollrath, Xinqian Hu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Mitochondrial DNA Programmed cell death lcsh:Medicine Retinal Pigment Epithelium Mechanistic Target of Rapamycin Complex 1 Senescence DNA Mitochondrial NDUFA9 Article Cell Line 03 medical and health sciences 0302 clinical medicine Medical research Cytotoxic T cell Humans Glycolysis lcsh:Science PI3K/AKT/mTOR pathway Membrane Potential Mitochondrial Multidisciplinary Chemistry lcsh:R Adenylate Kinase Cell Differentiation Epithelial Cells Retinal diseases 3. Good health Cell biology Mitochondria Didanosine Oxidative Stress 030104 developmental biology Cell culture Anaerobic glycolysis lcsh:Q sense organs 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-10 (2019) |
| ISSN: | 2045-2322 |
| Popis: | We investigated the effects of treating differentiated retinal pigment epithelial (RPE) cells with didanosine (ddI), which is associated with retinopathy in individuals with HIV/AIDS. We hypothesized that such treatment would cause depletion of mitochondrial DNA and provide insight into the consequences of degradation of RPE mitochondrial function in aging and disease. Treatment of differentiated ARPE-19 or human primary RPE cells with 200 µM ddI for 6–24 days was not cytotoxic but caused up to 60% depletion of mitochondrial DNA, and a similar reduction in mitochondrial membrane potential and NDUFA9 protein abundance. Mitochondrial DNA-depleted RPE cells demonstrated enhanced aerobic glycolysis by extracellular flux analysis, increased AMP kinase activation, reduced mTOR activity, and increased resistance to cell death in response to treatment with the oxidant, sodium iodate. We conclude that ddI-mediated mitochondrial DNA depletion promotes a glycolytic shift in differentiated RPE cells and enhances resistance to oxidative damage. Our use of ddI treatment to induce progressive depletion of mitochondrial DNA in differentiated human RPE cells should be widely applicable for other studies aimed at understanding RPE mitochondrial dysfunction in aging and disease. |
| Databáze: | OpenAIRE |
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