title: Up-regulation of plasma membrane-associated redox activities in neuronal cells lacking functional mitochondria.
abstract: Mitochondria-deficient cells (rho(o) cells) survive through enhanced glycolytic metabolism in the presence of pyruvate and uridine. The plasma membrane redox system (PMRS) contains several NAD(P)H-related enzymes and plays a key role in maintaining the levels of NAD(+)/NADH and reduced coenzyme Q. In this study, rho(o) cells were used to investigate how the PMRS is regulated under conditions of mitochondrial dysfunction. rho(o) cells exhibited a lower oxygen consumption rate and higher levels of lactate than parental cells, and were more sensitive to glycolysis inhibitors (2-deoxyglucose and iodoacetamide) than control cells. However, they were more resistant to H(2)O(2), consistent with increased catalase activity and decreased oxidative damage (protein carbonyls and nitrotyrosine). PM-associated redox enzyme activities were enhanced in rho(o) cells compared to those in control cells. Our data suggest that all PMRS enzymes and biomarkers tested are closely related to the ability of the PMs to maintain redox homeostasis. These results illustrate that an up-regulated PM redox activity can protect cells from oxidative stress as a result of an improved antioxidant capacity, and suggest a mechanism by which neurons adapt to conditions of impaired mitochondrial function.
authors.affiliation: Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
authors.forename: Dong-Hoon
authors.initials: DH
authors.lastname: Hyun
authors.forename: Nicole D
authors.initials: ND
authors.lastname: Hunt
authors.forename: Scott S
authors.initials: SS
authors.lastname: Emerson
authors.forename: Joe O
authors.initials: JO
authors.lastname: Hernandez
authors.forename: Mark P
authors.initials: MP
authors.lastname: Mattson
authors.forename: Rafael
authors.initials: R
authors.lastname: de Cabo
mesh_terms: D002374:Catalase / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D019069:Cell Respiration; D003067:Coenzymes; D003486:Cyanides / Q000494:pharmacology; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D009243:NAD / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000378:metabolism; D015854:Up-Regulation; D024502:alpha-Tocopherol / Q000378:metabolism
chemical_list: D003067:Coenzymes; D003486:Cyanides; D009243:NAD; D014451:Ubiquinone; D002374:Catalase; C024989:coenzyme Q10; D024502:alpha-Tocopherol