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MYTHO: a novel regulator of skeletal muscle autophagy and integrity

ABSTRACT: MYTHO: a novel regulator of skeletal muscle autophagy and integrity

PROVIDER: PRJNA923700 | ENA |

REPOSITORIES: ENA

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MYTHO: a novel regulator of skeletal muscle autophagy and integrity

Project description:Autophagy is a critical process in the regulation of muscle mass, function and integrity. The molecular mechanisms regulating autophagy are complex and still partly understood. Here, we identify and characterize a novel FoxO-dependent gene, d230025d16rik which we named Mytho (Macroautophagy and YouTH Optimizer), as a regulator of autophagy and skeletal muscle integrity in vivo. Mytho is significantly up-regulated in various mouse models of skeletal muscle atrophy. Short term depletion of MYTHO in mice attenuates muscle atrophy caused by fasting, denervation, cancer cachexia and sepsis. While MYTHO overexpression is sufficient to trigger muscle atrophy, MYTHO knockdown results in a progressive increase in muscle mass associated with a sustained activation of the mTORC1 signaling pathway. Prolonged MYTHO knockdown is associated with severe myopathic features, including impaired autophagy, muscle weakness, myofiber degeneration, and extensive ultrastructural defects, such as accumulation of autophagic vacuoles and tubular aggregates. Inhibition of the mTORC1 signaling pathway in mice using rapamycin treatment attenuates the myopathic phenotype triggered by MYTHO knockdown. Skeletal muscles from human patients diagnosed with myotonic dystrophy type 1 (DM1) display reduced Mytho expression, activation of the mTORC1 signaling pathway and impaired autophagy, raising the possibility that low Mytho expression might contribute to the progression of the disease. We conclude that MYTHO is a key regulator of muscle autophagy and integrity.

2023-01-20 | GSE222885 | GEO

MYTHO: a novel regulator of skeletal muscle autophagy and integrity [3 months]

Project description:MYTHO: a novel regulator of skeletal muscle autophagy and integrity mRNA expression data for the mouse muscle (n=4 per group) were obtained using Affymetrix Mouse Clariom S Assay (Affymetrix, Santa Carla, CA) according to the manufacturer’s recommendations.

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MYTHO: a novel regulator of skeletal muscle autophagy and integrity [3 weeks]

Project description:MYTHO: a novel regulator of skeletal muscle autophagy and integrity [3 weeks]

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MYTHO: a novel regulator of skeletal muscle autophagy and integrity [3 months]

Project description:MYTHO: a novel regulator of skeletal muscle autophagy and integrity [3 months]

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ATAD2 is a Novel Regulator of Myogenesis and Autophagy in Skeletal Muscles

Project description:MYTHO protein is a recently described novel regulator of autophagy and mass in skeletal muscles. Using immunoprecipitation assay, we found that the nuclear protein ATAD2 (ATPase family AAA domain containing 2) interacts with MYTHO protein in C2C12 myoblasts. The functional role of ATAD2 in skeletal muscle cells was assessed by using transient and stable Atad2 knockdown (KD) in C2C12 myoblasts. Atad2 KD significantly increased myoblast proliferation rate, S-phase entry, overall cell viability, and early differentiation into myotubes. However, Atad2 KD also elicited myotube atrophy and accumulation of autophagy-related proteins due to inhibition of autophagosome fusion with lysosomes and/or lysosome dysfunction. LAMP1 staining confirmed the presence of enlarged lysosomes in Atad2 KD cells. Additionally, genes involved in lysosome function and integrity including Rab7, Rab29, Nrbf2, and Cathepsin L were downregulated in Atad2 KD cells. Collectively, these results indicate that ATAD2 is a critical regulator of muscle cell proliferation, differentiation, and autophagy.

2026-04-27 | GSE328851 | GEO