MYTHO is a novel regulator of skeletal muscle autophagy and integrity


The study identifies a novel FoxO-dependent gene called Mytho (Macroautophagy and YouTH Optimizer) as a regulator of autophagy and skeletal muscle integrity in-vivo. The researchers show that Mytho is up-regulated in mouse models of skeletal muscle atrophy and that its short-term depletion in mice attenuates muscle atrophy through a variety of factors such as fasting, denervation, cancer cachexia, and sepsis. While MYTHO overexpression is found to induce muscle atrophy, MYTHO knockdown leads to an increase in muscle mass and sustained activation of the mTORC1 signaling pathway. In fact, prolonged MYTHO knockdown results in severe myopathic features, including impaired autophagy, muscle weakness, myofiber degeneration, and ultrastructural defects. Moreover, inhibition of the mTORC1 signaling pathway with rapamycin attenuates the myopathic phenotype associated with MYTHO knockdown. Together with these findings, the researchers delineate MYTHO as a crucial regulator of muscle autophagy and integrity, with potential implications for diseases like myotonic dystrophy type 1 (DM1).

This publication is featured in our October 2023 publication review. Check out the Cancer Cachexia-Induced Muscle Atrophy blog.