Up-regulation of plasma membrane-associated redox activities in neuronal cells lacking functional mitochondria

Dong Hoon Hyun, Nicole D. Hunt, Scott S. Emerson, Joe O. Hernandez, Mark P. Mattson, Rafael De Cabo

Research output: Contribution to journalArticle

Abstract

Mitochondria-deficient cells (ρo 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, ρo cells were used to investigate how the PMRS is regulated under conditions of mitochondrial dysfunction. ρo 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 H2O2, consistent with increased catalase activity and decreased oxidative damage (protein carbonyls and nitrotyrosine). PM-associated redox enzyme activities were enhanced in ρo 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.

Original languageEnglish (US)
Pages (from-to)1364-1374
Number of pages11
JournalJournal of Neurochemistry
Volume100
Issue number5
DOIs
StatePublished - Mar 2007
Externally publishedYes

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Mitochondria
Cell membranes
Oxidation-Reduction
Up-Regulation
Cell Membrane
NAD
Iodoacetamide
Ubiquinone
Oxidative stress
Uridine
Deoxyglucose
Enzyme activity
Biomarkers
Enzymes
Pyruvic Acid
Metabolism
Catalase
Neurons
Lactic Acid
Antioxidants

Keywords

  • Mitochondrial deficiency
  • Oxidative stress
  • Plasma membrane redox system

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Up-regulation of plasma membrane-associated redox activities in neuronal cells lacking functional mitochondria. / Hyun, Dong Hoon; Hunt, Nicole D.; Emerson, Scott S.; Hernandez, Joe O.; Mattson, Mark P.; De Cabo, Rafael.

In: Journal of Neurochemistry, Vol. 100, No. 5, 03.2007, p. 1364-1374.

Research output: Contribution to journalArticle

Hyun, Dong Hoon ; Hunt, Nicole D. ; Emerson, Scott S. ; Hernandez, Joe O. ; Mattson, Mark P. ; De Cabo, Rafael. / Up-regulation of plasma membrane-associated redox activities in neuronal cells lacking functional mitochondria. In: Journal of Neurochemistry. 2007 ; Vol. 100, No. 5. pp. 1364-1374.
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