Cited by 355Muscle Physiology and DisordersMitochondrial Function and PathologyAmyotrophic Lateral Sclerosis Research

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Denervation-induced skeletal muscle atrophy is associated with increased mitochondrial ROS production

Muller, Florian L., Song, Wook, Jang, Youngmok C., Liu, Yuhong, Sabia, Marian, Richardson, Arlan, Van Remmen, Holly·2007·American Journal of Physiology-Regulatory, Integrative and Comparative Physiology

DOI 10.1152/ajpregu.00767.2006

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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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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)
ORCID: Song, Wook
Liu, Yuhong
Richardson, Arlan
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
DOI: 10.1152/ajpregu.00767.2006
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 › Clinical 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

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Denervation-induced skeletal muscle atrophy is associated with increased mitochondrial ROS production

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