ArticleAntioxidants & redox signaling2013
Studies of mitochondrial and nonmitochondrial sources implicate nicotinamide adenine dinucleotide phosphate oxidase(s) in the increased skeletal muscle superoxide generation that occurs during contractile activity.
Article in Antioxidants & redox signaling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 160 papers.
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160 citing papers in PubMed, 273 citations in OpenAlex.
- Mitochondrial oxidative stress in skeletal muscle alters metabolic signaling responses to acute muscle contraction.Free radical biology & medicine · 2026Article
- A quantitative redox proteome of the human muscle response to exercise.bioRxiv : the preprint server for biology · 2026Article
- Exercise-related microRNAs in Caenorhabditis elegans regulate calcium homeostasis and mitochondrial dynamics: Conserved pathways, divergent microRNAs.The FEBS journal · 2026Article
- A decline in skeletal muscle NOX4 abrogates exercise-induced adaptive homeostasis and exacerbates biological aging.Science advances · 2026Article
- Update: Is exercise-induced oxidative stress a friend or foe?Sports medicine and health science · 2026Review
- Detecting oxidants in muscleRedox biochemistry and chemistry · 2026Article
- The role of sestrin2 in skeletal muscle regeneration after injury.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2026Article
- Skeletal muscle knockout of NAD(P)H oxidase 2 delays the development of isotonic diaphragm fatigue in mice.Free radical biology & medicine · 2025Article
- Redox-regulated signalling of adaptations to contractile activity in skeletal muscle: Implications for age-related muscle weakness.Experimental physiology · 2025Review
- Metformin suppresses the mitochondrial and transcriptional response to exercise, revealing a conserved BCL6B-associated angiogenic program.Journal of applied physiology (Bethesda, Md. : 1985) · 2025Article
- NADPH oxidases: redox regulation of cell homeostasis and disease.Physiological reviews · 2025Review
- Apocynin Mitigates Diabetic Muscle Atrophy by Lowering Muscle Triglycerides and Oxidative Stress.International journal of molecular sciences · 2025Article
- The cell origin of reactive oxygen species and its implication for evolutionary trade-offs.Open biology · 2025Review
- Leisure-Time Physical Activity, Sedentary Behavior, and Biological Aging: Evidence From Genetic Correlation and Mendelian Randomization Analyses.Scandinavian journal of medicine & science in sports · 2025Article
- Redox Control of Skeletal Muscle Function and Adaptations to Exercise.Advances in experimental medicine and biology · 2025Review
- Age-related changes of skeletal muscle metabolic response to contraction are also sex-dependent.The Journal of physiology · 2025Article
- Reactive oxygen species promote endurance exercise-induced adaptations in skeletal muscles.Journal of sport and health science · 2024Review
- Incretin-Based Therapies: A Promising Approach for Modulating Oxidative Stress and Insulin Resistance in Sarcopenia.Journal of bone metabolism · 2024Article
- Cognitive Dysfunction and Exercise: From Epigenetic to Genetic Molecular Mechanisms.Molecular neurobiology · 2024Review
- Retrotransposons in Werner syndrome-derived macrophages trigger type I interferon-dependent inflammation in an atherosclerosis model.Nature communications · 2024Article
100 more citing papers are in PubMed but not listed here.
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7 authors at 1 institution in 1 country.
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Abstract
aimsThe sources of cytosolic superoxide in skeletal muscle have not been defined. This study examined the subcellular sites that contribute to cytosolic superoxide in mature single muscle fibers at rest and during contractile activity.
resultsIsolated fibers from mouse flexor digitorum brevis loaded with superoxide and nitric-oxide-sensitive fluorescent probes, specific pathway inhibitors and immunolocalization techniques were used to identify subcellular sites contributing to cytosolic superoxide. Treatment with the electron transport chain complex III inhibitor, antimycin A, but not the complex I inhibitor, rotenone, caused increased cytosolic superoxide through release from the mitochondrial intermembrane space via voltage-dependent anion or Bax channels, but inhibition of these channels did not affect contraction-induced increases in cytosolic superoxide. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors decreased cytosolic superoxide at rest and following contractions. Protein and mRNA expression of NADPH oxidase subunits was demonstrated in single fibers. NOX2, NOX4, and p22(phox) subunits localized to the sarcolemma and transverse tubules; NOX4 was additionally expressed in mitochondria. Regulatory p40(phox) and p67(phox) proteins were found in the cytoplasm of resting fibers, but following contractions, p40(phox) appeared to translocate to the sarcolemma. INNOVATION: Superoxide and other reactive oxygen species generated by skeletal muscle are important regulators of muscle force production and adaptations to contractions. This study has defined the relative contribution of mitochondrial and cytosolic sources of superoxide within the cytosol of single muscle fibers at rest and during contractions.
conclusionMuscle mitochondria do not modulate cytosolic superoxide in skeletal muscle but NADPH oxidase is a major contributor both at rest and during contractions.
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