期刊
REDOX BIOLOGY
卷 1, 期 1, 页码 304-312出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.redox.2013.04.005
关键词
Superoxide; Hydrogen peroxide; Respiratory complexes; NADH; Ubiquinone; Cytochrome b
资金
- National Institutes of Health [P01 AG025901, PL1 AG032118, R01 AG03354, TL1 AG032116]
- Ellison Medical Foundation [AG-SS-2288-09]
- Glenn Foundation
- Carlsberg Foundation
- NATIONAL INSTITUTE ON AGING [TL1AG032116, PL1AG032118, R01AG033542, P01AG025901] Funding Source: NIH RePORTER
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 I-Q), 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 I-Q made little or no contribution, and production was shared between site IF, site [HQ and 2-oxoglutarate dehydrogenase. With palmitoylcarnitine as substrate, the flavin site in complex II (site [IF) 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. (C) 2013 The Authors. Published by Elsevier B.V. Open access under CC BY-NC-SA license.
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