The emerging roles of nicotinamide adenine dinucleotide phosphate oxidase 2 in skeletal muscle redox signaling and metabolism

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Significance: Skeletal muscle is a crucial tissue to whole-body locomotion and metabolic health. Reactive oxygen species (ROS) have emerged as intracellular messengers participating in both physiological and pathological adaptations in skeletal muscle. A complex interplay between ROS-producing enzymes and antioxidant networks exists in different subcellular compartments of mature skeletal muscle. Recent evidence suggests that NADPH oxidases (NOX) are a major source of contraction- and insulin-stimulated oxidants production, but may paradoxically also contribute to muscle insulin resistance and atrophy.

Recent advances: Pharmacological and molecular biological tools, including redox-sensitive probes and transgenic mouse models, have generated novel insights into compartmentalized redox signaling and suggested that NOX2 contributes to redox control of skeletal muscle metabolism.

Critical issues: Major outstanding questions in skeletal muscle include where NOX2 activation occurs under different conditions in health and disease, how NOX2 activation is regulated, how superoxide/ H2O2 generated by NOX2 reaches the cytosol, what the signaling mediators are downstream of NOX2, and the role of NOX2 for different physiological and pathophysiological processes.

Future directions: Future research should utilize and expand the current redox-signaling toolbox to clarify the NOX2-dependent mechanisms in skeletal muscle and determine whether the proposed functions of NOX2 in cells and animal models are conserved into man.

Original languageEnglish
JournalAntioxidants & Redox Signaling
Volume31
Issue number8
Pages (from-to)1371-1410
Number of pages40
ISSN1523-0864
DOIs
Publication statusPublished - 2019

    Research areas

  • Faculty of Science - Exercise, Skeletal muscle, Glucose metabolism, Insulin resistance, Atrophy

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