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Sites of reactive oxygen species generation by mitochondria oxidizing different substrates.

TitleSites of reactive oxygen species generation by mitochondria oxidizing different substrates.
Publication TypeJournal Article
Year of Publication2013
AuthorsQuinlan CL, Perevoshchikova IV, Hey-Mogensen M, Orr AL, Brand MD
JournalRedox Biol
Volume1
Pagination304-12
Date Published2013
ISSN2213-2317
KeywordsAnimals, Electron Transport Complex I, Electron Transport Complex III, Female, Glycerophosphates, Malates, Mitochondria, Muscle, Muscle, Skeletal, Palmitoylcarnitine, Rats, Rats, Wistar, Reactive Oxygen Species, Succinic Acid, Superoxides
Abstract

Mitochondrial radical production is important in redox signaling, aging and disease, but the relative contributions of different production sites are poorly understood. We analyzed the rates of superoxide/H2O2 production from different defined sites in rat skeletal muscle mitochondria oxidizing a variety of conventional substrates in the absence of added inhibitors: succinate; glycerol 3-phosphate; palmitoylcarnitine plus carnitine; or glutamate plus malate. In all cases, the sum of the estimated rates accounted fully for the measured overall rates. There were two striking results. First, the overall rates differed by an order of magnitude between substrates. Second, the relative contribution of each site was very different with different substrates. During succinate oxidation, most of the superoxide production was from the site of quinone reduction in complex I (site IQ), with small contributions from the flavin site in complex I (site IF) and the quinol oxidation site in complex III (site IIIQo). However, with glutamate plus malate as substrate, site IQ made little or no contribution, and production was shared between site IF, site IIIQo and 2-oxoglutarate dehydrogenase. With palmitoylcarnitine as substrate, the flavin site in complex II (site IIF) was a major contributor (together with sites IF and IIIQo), and with glycerol 3-phosphate as substrate, five different sites all contributed, including glycerol 3-phosphate dehydrogenase. Thus, the relative and absolute contributions of specific sites to the production of reactive oxygen species in isolated mitochondria depend very strongly on the substrates being oxidized, and the same is likely true in cells and in vivo.

DOI10.1016/j.redox.2013.04.005
Alternate JournalRedox Biol
PubMed ID24024165
PubMed Central IDPMC3757699
Grant ListPL1 AG032118 / AG / NIA NIH HHS / United States
P01 AG025901 / AG / NIA NIH HHS / United States
TL1AG032116 / AG / NIA NIH HHS / United States
AG-SS-2288-09 / AG / NIA NIH HHS / United States
R01AG03354 / AG / NIA NIH HHS / United States
TL1 AG032116 / AG / NIA NIH HHS / United States
R01 AG033542 / AG / NIA NIH HHS / United States
PL1AG032118 / AG / NIA NIH HHS / United States
P01AG025901 / AG / NIA NIH HHS / United States