Alterations in peroxisome-mitochondria interplay in skeletal muscle accelerate muscle dysfunction

Area of Science:

• Muscle physiology and aging research
• Cellular biology and organelle function
• Metabolic regulation

Background:

• Skeletal muscles are key metabolic regulators, but the role of peroxisomes is unclear.
• Peroxisomes are vital for lipid metabolism and reactive oxygen species clearance.
• Understanding peroxisome function is crucial for muscle health, especially during aging.

Purpose of the Study:

• To investigate the role of peroxisomes in skeletal muscle function.
• To determine the impact of peroxisome import deficiency on muscle health.
• To explore the relationship between peroxisomal function and aging in muscles.

Main Methods:

• Generated a muscle-specific transgenic mouse model with peroxisome import deficiency (Pex5 deletion).
• Assessed lipid metabolism, muscle force, and exercise performance.
• Analyzed mitochondrial structure, content, and function.
• Examined age-related changes and peroxisomal content during natural aging.

Main Results:

• Pex5 inhibition led to impaired lipid metabolism, reduced muscle force, and decreased exercise performance.
• Mitochondrial structure, content, and function were significantly altered.
• Peroxisome deficiency accelerated age-related muscle defects, including neuromuscular junction degeneration and atrophy.
• Natural aging in control mice showed a decline in muscle peroxisomal content.

Conclusions:

• Peroxisomal function is essential for maintaining skeletal muscle health and performance.
• Interplay between peroxisomes and mitochondria is critical for mitigating age-related muscle decline.
• Preserving peroxisomal function is a potential strategy to combat muscle aging.