Emerging role of TAK1 in the regulation of skeletal muscle mass

Bioessays. 2023 Apr;45(4):e2300003. doi: 10.1002/bies.202300003. Epub 2023 Feb 15.

Abstract

Maintenance of skeletal muscle mass and strength throughout life is crucial for heathy living and longevity. Several signaling pathways have been implicated in the regulation of skeletal muscle mass in adults. TGF-β-activated kinase 1 (TAK1) is a key protein, which coordinates the activation of multiple signaling pathways. Recently, it was discovered that TAK1 is essential for the maintenance of skeletal muscle mass and myofiber hypertrophy following mechanical overload. Forced activation of TAK1 in skeletal muscle causes hypertrophy and attenuates denervation-induced muscle atrophy. TAK1-mediated signaling in skeletal muscle promotes protein synthesis, redox homeostasis, mitochondrial health, and integrity of neuromuscular junctions. In this article, we have reviewed the role and potential mechanisms through which TAK1 regulates skeletal muscle mass and growth. We have also proposed future areas of research that could be instrumental in exploring TAK1 as therapeutic target for improving muscle mass in various catabolic conditions and diseases.

Keywords: TAK1; hypertrophy; neuromuscular junctions; protein synthesis; signaling; skeletal muscle atrophy.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Humans
  • Hypertrophy
  • MAP Kinase Kinase Kinases* / metabolism
  • Muscle, Skeletal*
  • Signal Transduction / physiology

Substances

  • MAP kinase kinase kinase 7
  • MAP Kinase Kinase Kinases