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dc.contributor.authorMoon, Sun Jin
dc.contributor.authorDong, Wentao
dc.contributor.authorStephanopoulos, Gregory N
dc.contributor.authorSikes, Hadley D
dc.date.accessioned2021-10-27T19:58:05Z
dc.date.available2021-10-27T19:58:05Z
dc.date.issued2020
dc.identifier.urihttps://hdl.handle.net/1721.1/134095
dc.description.abstract© 2020 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers. 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.
dc.language.isoen
dc.publisherWiley
dc.relation.isversionof10.1002/BTM2.10184
dc.rightsCreative Commons Attribution 4.0 International license
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceWiley
dc.titleOxidative pentose phosphate pathway and glucose anaplerosis support maintenance of mitochondrial NADPH pool under mitochondrial oxidative stress
dc.typeArticle
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemical Engineering
dc.relation.journalBioengineering & Translational Medicine
dc.eprint.versionFinal published version
dc.type.urihttp://purl.org/eprint/type/JournalArticle
eprint.statushttp://purl.org/eprint/status/PeerReviewed
dc.date.updated2021-06-22T16:34:39Z
dspace.orderedauthorsMoon, SJ; Dong, W; Stephanopoulos, GN; Sikes, HD
dspace.date.submission2021-06-22T16:34:42Z
mit.journal.volume5
mit.journal.issue3
mit.licensePUBLISHER_CC
mit.metadata.statusAuthority Work and Publication Information Needed


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