The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
Runx1 prevents wasting, myofibrillar disorganization, and autophagy of skeletal muscle
Open accessAbstract
Disruptions in the use of skeletal muscle lead to muscle atrophy. After short periods of disuse, muscle atrophy is reversible, and even after prolonged periods of inactivity, myofiber degeneration is uncommon. The pathways that regulate atrophy, initiated either by peripheral nerve damage, immobilization, aging, catabolic steroids, or cancer cachexia, however, are poorly understood. Previously, we found that Runx1 (AML1), a DNA-binding protein that is homologous to Drosophila Runt and has critical roles in hematopoiesis and leukemogenesis, is poorly expressed in innervated muscle, but strongly induced in muscle shortly after denervation. To determine the function of Runx1 in skeletal muscle, we generated mice in which Runx1 was selectively inactivated in muscle. Here, we show that Runx1 is required to sustain muscle by preventing denervated myofibers from undergoing myofibrillar disorganization and autophagy, structural defects found in a variety of congenital myopathies. We find that only 29 genes, encoding ion channels, signaling molecules, and muscle structural proteins, depend upon Runx1 expression, suggesting that their misregulation causes the dramatic muscle wasting. These findings demonstrate an unexpected role for electrical activity in regulating muscle wasting, and indicate that muscle disuse induces compensatory mechanisms that limit myofiber atrophy. Moreover, these results suggest that reduced muscle activity could cause or contribute to congenital myopathies if Runx1 or its target genes were compromised.
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“skeletal muscle denervation causes neurogenic atrophy and may activate autophagy;”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [472]
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“Conversely, genetic ablation of RUNX1 disinhibits autophagy and worsens atrophy [472].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [472]
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“such a protective response (mounted by the transcription factor RUNX1) limits muscle wasting after denervation by suppressing autophagy.”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [472]
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Metadata
- Authors
- Wang, X., Blagden, C., Fan, J., Nowak, S. J., Taniuchi, I., Littman, D. R., & Burden, S. J.
- Affiliations
- Howard Hughes Medical Institute (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2005-07-15
- Volume
- 19
- Issue
- 14
- Pages
- 1715-1722
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC1176009
- OpenAlex
- W2099304566
- Cited by
- 177
- References
- 43
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 9 · 2023: 6 · 2022: 13 · 2021: 9 · 2020: 11 · 2019: 4 · 2018: 3 · 2017: 4 · 2016: 9 · 2015: 14 · 2014: 14 · 2013: 8 · 2012: 17
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health
- National Institute of Mental Health
- National Institute of Neurological Disorders and Stroke (R01NS027963)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Genetics (clinical) › Neurogenetic and Muscular Disorders Research
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Meat and Animal Product Quality
- Keywords
- RUNX1, skeletal muscle atrophy, denervation, myofibrillar disorganization, autophagy, myofiber degeneration, congenital myopathy, muscle electrical activity, compensatory mechanisms, ion channels, muscle structural proteins
- MeSH terms
- Forkhead Box Protein O1, Animals, Autophagy, DNA-Binding Proteins, Male, Mice, Mutant Strains, Mice, Transgenic, Models, Biological, Muscle Denervation, Muscular Atrophy, Myofibrils, Proto-Oncogene Proteins, Transcription Factors, Gene Expression, Muscle, Skeletal, Core Binding Factor Alpha 2 Subunit, Mice, Forkhead Transcription Factors
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