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The importance of the thioredoxin system in muscle mitochondrial reactive oxygen species metabolism (1159.10)
Author(s) -
Treberg Jason,
Banh Sheena,
Sotiri Emianka,
Zacharias Pamela,
Tamanhid
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1159.10
Subject(s) - auranofin , thioredoxin reductase , thioredoxin , reactive oxygen species , mitochondrion , glutathione , biochemistry , skeletal muscle , chemistry , mitochondrial ros , microbiology and biotechnology , bioenergetics , glutathione reductase , nad+ kinase , glutathione peroxidase , oxidative stress , biology , enzyme , endocrinology , rheumatoid arthritis , immunology
Mitochondria are widely recognized as a potential source of reactive oxygen species (ROS); however, mitochondria also possess a strong capacity for ROS consumption that is often underappreciated. In skeletal muscle the glutathione and thioredoxin based peroxidase systems are likely the major H2O2 consumption pathways. Here we demonstrate the thioredoxin‐based pathway is the major H2O2 consumer in isolated rat skeletal muscle mitochondria. Unlike 1‐chloro‐2,4‐dinitrobenzene, the thioredoxin reductase inhibitor auranofin does not elevate ROS production in disrupted membranes that are devoid of the capacity to consume H2O2. Inhibition of thioredoxin reductase with auranofin leads to a marked increase in apparent ROS production but no change in mitochondrial bioenergetic characteristics (oxygen consumption, membrane potential, %NAD(P)H). Moreover, auranofin also inhibits the capacity for H2O2 consumption by isolated mitochondria and does not appear to act through the inhibition of the glutathione reduction system. We conclude that the apparent increase is H2O2 release by treatment with auranofin is due to impaired matrix level thioredoxin‐dependent H2O2 consumption and not reflective of an activation of ROS production. Grant Funding Source : Supported by Canada Research Chairs (CRC), CFI, Manitoba Research and Innovation Fund and NSERC