Oxidative pentose phosphate pathway and glucose anaplerosis support maintenance of mitochondrial NADPH pool under mitochondrial oxidative stress
Autor: | Wentao Dong, Hadley D. Sikes, Sun Jin Moon, Gregory Stephanopoulos |
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Rok vydání: | 2020 |
Předmět: |
Research Report
Antioxidant medicine.medical_treatment lcsh:Biotechnology Biomedical Engineering Pharmaceutical Science hydrogen peroxide Pentose phosphate pathway Mitochondrion medicine.disease_cause chemistry.chemical_compound lcsh:TP248.13-248.65 medicine NADPH oxidative stress lcsh:Chemical engineering Hydrogen peroxide redox kinetic model NADPH sensor Chemistry lcsh:RM1-950 lcsh:TP155-156 Research Reports 13c glucose mitochondria NADPH metabolism Cytosol lcsh:Therapeutics. Pharmacology Biochemistry Oxidative stress Biotechnology |
Zdroj: | Bioengineering & Translational Medicine, Vol 5, Iss 3, Pp n/a-n/a (2020) Bioengineering & Translational Medicine |
ISSN: | 2380-6761 |
Popis: | Mitochondrial NADPH protects cells against mitochondrial oxidative stress by serving as an electron donor to antioxidant defense systems. However, due to technical challenges, it still remains unknown as to the pool size of mitochondrial NADPH, its dynamics, and NADPH/NADP+ ratio. Here, we have systemically modulated production rates of H2O2 in mitochondria and assessed mitochondrial NADPH metabolism using iNap sensors, 13C glucose isotopic tracers, and a mathematical model. Using sensors, we observed decreases in mitochondrial NADPH caused by excessive generation of mitochondrial H2O2, whereas the cytosolic NADPH was maintained upon perturbation. We further quantified the extent of mitochondrial NADPH/NADP+ based on the mathematical analysis. Utilizing 13C glucose isotopic tracers, we found increased activity in the pentose phosphate pathway (PPP) accompanied small decreases in the mitochondrial NADPH pool, whereas larger decreases induced both PPP activity and glucose anaplerosis. Thus, our integrative and quantitative approach provides insight into mitochondrial NADPH metabolism during mitochondrial oxidative stress. |
Databáze: | OpenAIRE |
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