Denervation-Induced Skeletal Muscle Atrophy Is Associated with Increased Mitochondrial Ros Production
Abstract
Reactive oxygen species (ROS), especially mitochondrial ROS, are postulated to play a significant role in muscle atrophy. We report a dramatic increase in mitochondrial ROS generation in three conditions associated with muscle atrophy: in aging, in mice lacking CuZn-SOD (Sod1(-/-)), and in the neurodegenerative disease, amyotrophic lateral sclerosis (ALS). ROS generation in muscle mitochondria is nearly threefold higher in 28- to 32-mo-old than in 10-mo-old mice and is associated with a 30% loss in gastrocnemius mass. In Sod1(-/-) mice, muscle mitochondrial ROS production is increased >100% in 20-mo compared with 5-mo-old mice along with a >50% loss in muscle mass. ALS G93A mutant mice show a 75% loss of muscle mass during disease progression and up to 12-fold higher muscle mitochondrial ROS generation. In a second ALS mutant model, H46RH48Q mice, ROS production is approximately fourfold higher than in control mice and is associated with a less dramatic loss (30%) in muscle mass. Thus ROS production is strongly correlated with the extent of muscle atrophy in these models. Because each of the models of muscle atrophy studied are associated to some degree with a loss of innervation, we were interested in determining whether denervation plays a role in ROS generation in muscle mitochondria isolated from hindlimb muscle following surgical sciatic nerve transection. Seven days post-denervation, muscle mitochondrial ROS production increased nearly 30-fold. We conclude that enhanced generation of mitochondrial ROS may be a common factor in the mechanism underlying denervation-induced atrophy.
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Enhanced generation of mitochondrial ROS may be a common factor in denervation-induced atrophy.
“Enhanced generation of mitochondrial ROS may be a common factor in the mechanism underlying denervation-induced atrophy [15].”
From Nutraceuticals in the Prevention and Treatment of the Muscle Atrophy (2021) · cites this paper as [15]
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- Authors
- Muller, F. L., Song, W., Jang, Y. C., Liu, Y., Sabia, M., Richardson, A., & Van Remmen, H.
- Affiliations
- Seoul National University (KR)
- The University of Texas at San Antonio Health Science Center (US)
- Venue
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Publisher
- American Physiological Society
- Published
- 2007-09
- Volume
- 293
- Issue
- 3
- Pages
- R1159-R1168
- ISSN
- 0363-6119 (ISSN-L)
- 1522-1490
- OpenAlex
- W2137182040
- Cited by
- 355
- References
- 88
- Citations by year
- 2026: 11 · 2025: 14 · 2024: 16 · 2023: 14 · 2022: 35 · 2021: 23 · 2020: 29 · 2019: 23 · 2018: 25 · 2017: 19 · 2016: 26 · 2015: 18 · 2014: 13 · 2013: 20 · 2012: 16
- FWCI
- 5.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (5T3 AG 021890 02, P01 AG-20591, P01AG020591, T32AG021890)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- skeletal muscle atrophy, denervation, mitochondrial reactive oxygen species, oxidative stress, sciatic nerve transection, aging, amyotrophic lateral sclerosis, muscle mass loss, hindlimb muscles
- MeSH terms
- Superoxide Dismutase-1, Amyotrophic Lateral Sclerosis, Animals, Female, Mice, Inbred C57BL, Mitochondria, Muscle, Muscle Denervation, Muscular Atrophy, Organ Size, Oxygen Consumption, Sciatic Nerve, Superoxide Dismutase, Reactive Oxygen Species, Mice, Knockout, Oxidative Stress, Muscle, Skeletal, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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