Spermidine-eIF5A axis is essential for muscle stem cell activation via translational control

Area of Science:

• Muscle stem cell biology
• Metabolic regulation of cell activation
• Regenerative medicine

Background:

• Adult skeletal muscle stem cells, or satellite cells (SCs), are quiescent but activate upon injury.
• The precise mechanisms governing quiescent SC activation remain poorly understood.
• Identifying key regulators of SC activation is critical for understanding muscle repair.

Purpose of the Study:

• To investigate the metabolic regulation of skeletal muscle stem cell activation.
• To identify specific metabolites that promote SC activation and muscle regeneration.
• To elucidate the molecular mechanisms underlying spermidine-mediated SC activation.

Main Methods:

• Targeted metabolomics to identify regulatory metabolites.
• In vivo studies using SC-specific eIF5A-knockout and Myod-knockout mice.
• Analysis of protein translation and muscle regeneration capacity.

Main Results:

• Spermidine was identified as a key metabolite promoting SC activation and muscle regeneration in mice.
• Spermidine activates SCs by inducing hypusinated eIF5A, which is essential for MyoD translation.
• Depletion of eIF5A in SCs impairs spermidine-mediated activation and muscle regeneration.

Conclusions:

• A novel mechanism for SC activation involving the spermidine-eIF5A-MyoD translation axis has been defined.
• This pathway is essential for effective muscle regeneration.
• The spermidine-eIF5A axis presents a potential therapeutic target for treating muscular diseases.