title: The Measurement of Reversible Redox Dependent Post-translational Modifications and Their Regulation of Mitochondrial and Skeletal Muscle Function.
abstract: Mitochondrial oxidative stress is a common feature of skeletal myopathies across multiple conditions; however, the mechanism by which it contributes to skeletal muscle dysfunction remains controversial. Oxidative damage to proteins, lipids, and DNA has received the most attention, yet an important role for reversible redox post-translational modifications (PTMs) in pathophysiology is emerging. The possibility that these PTMs can exert dynamic control of muscle function implicates them as a mechanism contributing to skeletal muscle dysfunction in chronic disease. Herein, we discuss the significance of thiol-based redox dependent modifications to mitochondrial, myofibrillar, and excitation-contraction (EC) coupling proteins with an emphasis on how these changes could alter skeletal muscle performance under chronically stressed conditions. A major barrier to a better mechanistic understanding of the role of reversible redox PTMs in muscle function is the technical challenges associated with accurately measuring the changes of site-specific redox PTMs. Here we will critically review current approaches with an emphasis on sample preparation artifacts, quantitation, and specificity. Despite these challenges, the ability to accurately quantify reversible redox PTMs is critical to understanding the mechanisms by which mitochondrial oxidative stress contributes to skeletal muscle dysfunction in chronic diseases.
authors.affiliation: Department of Radiology, University of Washington Seattle, WA, USA.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Kramer
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory Richland, WA, USA.
authors.forename: Jicheng
authors.initials: J
authors.lastname: Duan
authors.affiliation: Biological Sciences Division, Pacific Northwest National Laboratory Richland, WA, USA.
authors.forename: Wei-Jun
authors.initials: WJ
authors.lastname: Qian
authors.affiliation: Department of Radiology, University of Washington Seattle, WA, USA ; Department of Bioengineering, University of Washington Seattle, WA, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Marcinek
keywords: glutathionylation; mitochondria; myofibrils; post-translational modification; redox signaling; skeletal muscle