The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
FoxO3 Controls Autophagy in Skeletal Muscle In Vivo
Open accessAbstract
Autophagy allows cell survival during starvation through the bulk degradation of proteins and organelles by lysosomal enzymes. However, the mechanisms responsible for the induction and regulation of the autophagy program are poorly understood. Here we show that the FoxO3 transcription factor, which plays a critical role in muscle atrophy, is necessary and sufficient for the induction of autophagy in skeletal muscle in vivo. Akt/PKB activation blocks FoxO3 activation and autophagy, and this effect is not prevented by rapamycin. FoxO3 controls the transcription of autophagy-related genes, including LC3 and Bnip3, and Bnip3 appears to mediate the effect of FoxO3 on autophagy. This effect is not prevented by proteasome inhibitors. Thus, FoxO3 controls the two major systems of protein breakdown in skeletal muscle, the ubiquitin-proteasomal and autophagic/lysosomal pathways, independently. These findings point to FoxO3 and Bnip3 as potential therapeutic targets in muscle wasting disorders and other degenerative and neoplastic diseases in which autophagy is involved.
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In the citing paper
“Autophagy-promoting effects of AMPK are most evident in cells cultured in a complete medium with serum and amino acids, where cargo sequestration is otherwise largely suppressed [662].”
From Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1 (2021) · cites this paper as [662]
In the citing paper
“In liver cells, AMPK suppresses autophagy at the level of cargo sequestration, as indicated by the rapid sequestration-inhibitory effects of a variety of AMPK activators”
From Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1 (2021) · cites this paper as [662]
In the citing paper
“whereas it appears to stimulate autophagy in many other cell types, including fibroblasts, colon carcinoma cells and skeletal muscle [656-665]”
From Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1 (2021) · cites this paper as [662]
In the citing paper
“FoxO family of transcription factors (FoxO1, FoxO3, and FoxO4) are critical mediators of the catabolic response during atrophy [9, 15, 16].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [15]
In the citing paper
“The activation of mitophagy triggered by the transient overexpression of BNIP3 and BNIP3L induce muscle atrophy [15, 152].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [15]
In the citing paper
“In agreement, transient inhibition of BNIP3 in skeletal muscle partially protects from muscle loss induced by fasting, FoxO3, and FGF21 overexpression [15, 152, 212].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [15]
In the citing paper
“we focused in the other muscle major degradative pathway, the autophagy lysosomal system, which is essential for muscle homeostasis.38, 39”
From Fibroblast growth factor 21 controls mitophagy and muscle mass (2019) · cites this paper as [38]
In the citing paper
“we already demonstrated that Bnip3 inhibition reduces autophagosome formation and protects against muscle loss during atrophy,25, 38”
From Fibroblast growth factor 21 controls mitophagy and muscle mass (2019) · cites this paper as [38]
In the citing paper
“Starvation-related atrophy is also associated with upregulated autophagy, which in turn is controlled by the transcription factor FOXO3 and is independent of MTOR activity [473].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [473]
In the citing paper
“autophagy is critical for maintaining normal homeostasis of muscle mass in physiological and pathological conditions30,47–49.”
From Disuse-associated loss of the protease Lonp1 in muscle impairs mitochondrial function and causes reduced skeletal muscle mass and strength (2022) · cites this paper as [30]
In the citing paper
“Excessive activation of autophagy aggravates muscle wasting by removing portion of cytoplasm, proteins, and organelles30,50,51”
From Disuse-associated loss of the protease Lonp1 in muscle impairs mitochondrial function and causes reduced skeletal muscle mass and strength (2022) · cites this paper as [30]
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Metadata
- Authors
- Mammucari, C., Milan, G., Romanello, V., Masiero, E., Rudolf, R., Del Piccolo, P., Burden, S. J., Di Lisi, R., Sandri, C., Zhao, J., Goldberg, A. L., Schiaffino, S., & Sandri, M.
- Affiliations
- University of Padua (IT)
- Veneto Institute of Molecular Medicine (IT)
- New York University (US)
- Harvard University (US)
- Corresponding author
- Sandri, Marco
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2007-12
- Volume
- 6
- Issue
- 6
- Pages
- 458-471
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2025192214
- Cited by
- 1,953
- References
- 42
- Citations by year
- 2026: 54 · 2025: 76 · 2024: 88 · 2023: 82 · 2022: 114 · 2021: 127 · 2020: 111 · 2019: 128 · 2018: 119 · 2017: 127 · 2016: 123 · 2015: 124 · 2014: 123 · 2013: 142 · 2012: 118
- FWCI
- 47.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS27963, R01NS027963)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR055255, R01AR055027)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › FOXO transcription factor regulation
- Keywords
- FOXO3, autophagy, skeletal muscle, Akt signaling, BNIP3, LC3, muscle atrophy, protein degradation, transcriptional regulation, rapamycin
- MeSH terms
- Forkhead Box Protein O3, Animals, Autophagy, Gene Expression Regulation, Lysosomes, Membrane Proteins, Mice, Transgenic, Microtubule-Associated Proteins, Models, Biological, Muscular Atrophy, Protein Kinases, Muscle, Skeletal, Mitochondrial Proteins, Ubiquitin, RNA Interference, Proteasome Endopeptidase Complex, Proto-Oncogene Proteins c-akt, Mice, Forkhead Transcription Factors, TOR Serine-Threonine Kinases
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